REGULATOR OF G SIGNALING 16 IS A MARKER FOR THE DISTINCT ER STRESS STATE ASSOCIATED WITH AGGREGATED MUTANT α1-ANTITRYPSIN Z IN THE

CLASSICAL FORM OF α1-ANTITRYPSIN DEFICIENCY Tunda Hidvegi1, Karoly Mirnics2, Pamela Hale1, Michael Ewing1, Caroline Beckett1 and David H

Perlmutter1 Supplemental Material Supp Figure 1. Networks of genes regulated during the response to accumulation of mutant ATZ. These networks were identified by Ingenuity Pathway analysis and are displayed here exactly as described in the legend to Figure 3. The 2 most significantly powered networks are shown in Figure 3 and here we show 3 of the other 9 significant networks identified by the analysis. The names of the genes that correspond to the abbreviations can be found in Supplementary Table 1. Supp Table 1. Full list of all genes significantly altered in expression. The abbreviations correspond to the Affymetrix ID. FC, fold change. *, multiple hits (fold change represents the change of greatest magnitude) Supp Table 2. Biological themes describing changes in gene expression profile as determined by the Affymetrix GO browser. Supp Table 3. Selected genes upregulated in expression during response to accumulation of mutant ATZ Supp Table 4. Selected genes downregulated in expression during response to accumulation of mutant ATZ

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Supplementary Table 1: Complete list of significant changes in gene expression

Probe Names Gene Name FC Adjusted p-value Group Gene Symbol

1425837_a_at CCR4 carbon catabolite repression 4-like (S. cerevisiae) 9.6 0.0E+00 adult Ccrn4l 1438211_s_at D site albumin promoter binding protein* 9.1 0.00E+00 both Dbp 1426516_a_at lipin 1* 6.4 0.0E+00 adult Lpin1 1420984_at phosphatidylcholine transfer protein* 6.0 0.00E+00 juv Pctp

1419094_at cytochrome P450, family 2. subfamily c, polypeptide 37 /// cytochrome P450, family 2, subfamily c, polypeptide 50 /// cytochrome P450 /// similar to cytochrome P450

5.6 5.0E-12 adult Cyp2c37 /// Cyp2c50 /// Cyp2c54

1451190_a_at SH3-binding kinase 1 5.5 0.0E+00 adult Sbk1 1426037_a_at regulator of G-protein signaling 16* 5.4 0.0E+00 both Rgs16 1424598_at DEAD (Asp-Glu-Ala-Asp) box polypeptide 6 4.7 0.0E+00 adult Ddx6 1417168_a_at ubiquitin specific protease 2* 4.6 0.00E+00 both Usp2

1436898_at splicing factor proline/glutamine rich (polypyrimidine tract binding protein associated) 4.0 0.0E+00 adult Sfpq

1424126_at aminolevulinic acid synthase 1* 4.0 0.0E+00 adult Alas1 1424778_at receptor accessory protein 3 3.5 1.0E-11 adult Reep3 1451548_at BC027189 unkonwn protein 3.4 0.00E+00 juv --- 1448667_x_at transducer of ERBB2, 2 3.3 9.2E-10 adult Tob2 1442025_a_at sequence AI467657 3.0 0.0E+00 adult AI467657 1421087_at period homolog 3 (Drosophila) 3.0 1.71E-38 both Per3 1416958_at nuclear receptor subfamily 1, group D, member 2 3.0 3.04E-20 juv Nr1d2 1454838_s_at expressed sequence AW548124 3.0 1.7E-07 adult AW548124 1419523_at cytochrome P450, family 3, subfamily a, polypeptide 13 3.0 0.0E+00 adult Cyp3a13 1452837_at lipin 2* 3.0 1.2E-10 adult Lpin2 1437288_at inositol monophosphatase domain containing 1 3.0 2.6E-06 adult Impad1

1419717_at sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3E 3.0 0.0E+00 adult Sema3e

1435129_at protein tyrosine phosphatase 4a2 3.0 3.64E-20 juv Ptp4a2

1451716_at v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B (avian) 3.0 1.9E-06 adult Mafb

1451989_a_at microtubule-associated protein, RP/EB family, member 2 2.9 2.97E-17 juv Mapre2 1423439_at phosphoenolpyruvate carboxykinase 1, cytosolic 2.9 6.47E-16 juv Pck1 1425480_at CCR4-NOT transcription complex, subunit 6-like 2.9 2.3E-07 adult Cnot6l 1438955_x_at peptidylprolyl isomerase F (cyclophilin F) 2.8 3.9E-10 adult Ppif 1419816_s_at ERBB receptor feedback inhibitor 1 2.7 5.8E-08 adult Errfi1 1448265_x_at epithelial V-like antigen 1 2.7 8.1E-06 adult Eva1

1425514_at phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha) 2.7 2.5E-11 adult Pik3r1

1417991_at deiodinase, iodothyronine, type I 2.7 1.66E-13 juv Dio1

1416029_at Kruppel-like factor 10 (was:TGFB inducible early growth response 1) 2.7 0.0E+00 adult Klf10

1437667_a_at BTB and CNC homology 2 2.7 1.6E-04 adult Bach2

1456590_x_at aldo-keto reductase family 1, member B3 (aldose reductase) 2.7 3.6E-10 adult Akr1b3

1420941_at regulator of G-protein signaling 5 2.6 6.6E-06 adult Rgs5 1426583_at activating transcription factor 2 2.6 1.7E-05 adult Atf2 1448568_a_at solute carrier family 20, member 1 2.6 1.0E-11 adult Slc20a1 1452416_at interleukin 6 receptor, alpha 2.6 1.8E-03 adult Il6ra 1433662_s_at tissue inhibitor of metalloproteinase 2 2.6 4.5E-04 adult Timp2 1456466_x_at ataxin 10 2.6 6.4E-06 adult Atxn10 1417904_at DNA cross-link repair 1A, PSO2 homolog (S. cerevisiae) 2.6 1.1E-04 both Dclre1a 1428022_at lipocalin 13 2.5 1.00E-11 juv Lcn13 1416773_at wee 1 homolog (S. pombe) 2.5 5.5E-05 adult Wee1 1418655_at beta-1,4-N-acetyl-galactosaminyl transferase 1 2.5 2.01E-11 juv B4galnt1 1449089_at nuclear receptor interacting protein 1 2.5 4.6E-07 adult Nrip1 1456199_x_at RAN binding protein 9 2.4 3.2E-04 adult Ranbp9

1422230_s_at cytochrome P450, family 2, subfamily a, polypeptide 4 /// cytochrome P450, family 2, subfamily a, polypeptide 5 2.4 2.51E-11 juv Cyp2a4 /// Cyp2a5

1437100_x_at proviral integration site 3 2.4 1.8E-06 adult Pim3 1449315_at odd Oz/ten-m homolog 3 (Drosophila) 2.4 1.1E-04 adult Odz3 1460316_at acyl-CoA synthetase long-chain family member 1 2.4 3.9E-04 adult Acsl1 1418180_at trans-acting transcription factor 1 2.4 1.9E-03 adult Sp1 1451154_a_at CUG triplet repeat, RNA binding protein 2 2.4 2.0E-04 adult Cugbp2 1435626_a_at homocysteine-inducible, endoplasmic reticulum stress- 2.4 1.3E-05 adult Herpud1

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inducible, ubiquitin-like domain member 1 1451638_s_at armadillo repeat containing protein 2.3 1.0E-03 adult Armc1

1456377_x_at LIM domain containing 2 /// similar to epithelial protein lost in neoplasm 2.3 3.5E-08 adult Limd2

1420342_at ganglioside-induced differentiation-associated-protein 10 2.3 3.2E-04 adult Gdap10 1425332_at zinc finger protein 106 2.3 1.7E-04 adult Zfp106 1455961_at AV174022 kidney androgen regulated protein 2.3 8.7E-03 adult --- 1416779_at serum deprivation response 2.3 3.6E-04 adult Sdpr 1418025_at basic helix-loop-helix domain containing, class B2 2.3 2.2E-04 adult Bhlhb2

1455457_at cytochrome P450, family 2, subfamily c, polypeptide 50 /// cytochrome P450 2.3 2.4E-06 adult Cyp2c50 /// Cyp2c54

1420772_a_at TSC22 domain family 3 2.3 9.1E-03 adult Tsc22d3 1422493_at coproporphyrinogen oxidase* 2.3 1.4E-02 adult Cpox

1439122_at BF226295 DEAD (aspartate-glutamate-alanine-aspartate) box polypeptide 6 2.2 1.5E-03 adult ---

1427000_at hepatic nuclear factor 4, alpha 2.2 1.1E-02 adult Hnf4a 1416953_at connective tissue growth factor 2.2 3.7E-05 adult Ctgf 1426432_a_at solute carrier family 4 (anion exchanger), member 4 2.2 7.1E-05 adult Slc4a4 1423635_at bone morphogenetic protein 2 2.2 2.1E-03 adult Bmp2

1422648_at solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 2.2 1.4E-06 both Slc7a2

1417084_at eukaryotic translation initiation factor 4E binding protein 2 2.2 4.3E-02 adult Eif4ebp2

1417753_at polycystic kidney disease 2 2.2 8.4E-03 adult Pkd2 1448944_at neuropilin 1 2.2 8.8E-04 adult Nrp1 1448908_at phosphatidic acid phosphatase type 2B 2.2 4.2E-05 adult Ppap2b 1424815_at glycogen synthase 2 /// similar to glycogen synthase 2 2.2 8.7E-06 adult Gys2 1425270_at kinesin family member 1B 2.1 1.3E-05 adult Kif1b 1422881_s_at synaptophysin-like protein 2.1 9.6E-04 adult Sypl 1437714_x_at Ubiquitin specific peptidase 14 2.1 6.9E-03 adult Usp14 1424350_s_at lysophosphatidylglycerol acyltransferase 1 2.1 2.7E-02 adult Lpgat1 1452231_x_at interferon activated gene 203* 2.1 4.85E-09 juv Ifi203 1456054_a_at pumilio 1 (Drosophila) 2.1 5.3E-04 adult Pum1 1416432_at 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 2.1 8.1E-03 both Pfkfb3 1428942_at metallothionein 2 2.1 1.41E-08 juv Mt2 1421230_a_at Musashi homolog 2 (Drosophila) 2.1 2.0E-04 adult Msi2 1459211_at GLI-Kruppel family member GLI2 2.1 2.53E-08 juv Gli2 1421852_at potassium channel, subfamily K, member 5 2.0 1.3E-02 adult Kcnk5 1434326_x_at coronin, actin binding protein, 2B 2.0 8.6E-04 adult Coro2b 1438952_x_at TAR (HIV) RNA binding protein 2 2.0 3.23E-08 juv Tarbp2 1424175_at thyrotroph embryonic factor 2.0 4.2E-05 adult Tef 1421830_at adenylate kinase 3 alpha-like 1 1.9 4.96E-07 juv Ak3l1 1421011_at hydroxysteroid (17-beta) dehydrogenase 11 1.9 1.13E-06 juv Hsd17b11 1460258_at leukocyte cell derived chemotaxin 1 1.9 4.84E-06 juv Lect1 1449565_at cytochrome P450, family 2, subfamily g, polypeptide 1 1.8 6.17E-06 juv Cyp2g1 1421818_at B-cell leukemia/lymphoma 6 1.8 7.76E-06 juv Bcl6 1417896_at tight junction protein 3 -1.8 8.63E-03 juv Tjp3 1460673_at folylpolyglutamyl synthetase -1.9 1.03E-02 juv Fpgs

1423269_a_at neural precursor cell expressed, developmentally down-regulated gene 4-like -1.9 1.07E-02 juv Nedd4l

1424318_at RIKEN cDNA 1110067D22 gene -1.9 1.08E-02 juv 1110067D22Rik 1416630_at inhibitor of DNA binding 3 -1.9 1.32E-02 juv Id3 1452431_s_at histocompatibility 2, class II antigen E alpha -2.0 2.1E-06 adult H2-Aa H2-Ea 1418603_at arginine vasopressin receptor 1A -2.0 6.4E-05 both Avpr1a 1450033_a_at signal transducer and activator of transcription 1 -2.0 2.1E-02 adult Stat1 1424999_at RIKEN cDNA 1700022C21 gene -2.0 3.1E-03 adult 1700022C21Rik 1416580_a_at STIP1 homology and U-Box containing protein 1 -2.0 3.8E-02 adult Stub1 1448158_at syndecan 1 -2.0 2.5E-03 adult Sdc1 1421903_at intersex-like (Drosophila) -2.0 3.4E-02 adult Ixl 1431304_a_at transmembrane protein 183A -2.0 1.3E-02 adult Tmem183a 1426679_at zinc finger protein 706 -2.0 4.3E-02 adult Zfp706 1453195_at serologically defined colon cancer antigen 3 -2.0 2.1E-03 adult Sdccag3 1423447_at caseinolytic peptidase X (E.coli) -2.0 1.35E-02 juv Clpx 1460323_at threonyl-tRNA synthetase -2.0 4.3E-04 adult Tars

1451366_at COP9 (constitutive photomorphogenic) homolog, subunit 6 (Arabidopsis thaliana) -2.0 2.7E-02 adult Cops6

1417014_at heat shock protein 8 -2.0 3.4E-03 adult Hspb8

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1428372_at suppression of tumorigenicity 5 -2.0 1.53E-02 juv St5 1416770_at serine/threonine kinase 25 (yeast) -2.0 4.1E-02 adult Stk25 1417161_at CDK2-associated protein 2 -2.0 7.6E-03 adult Cdk2ap2 1421812_at TAP binding protein* -2.0 4.0E-06 adult Tapbp

1417063_at complement component 1, q subcomponent, beta polypeptide -2.0 1.9E-03 adult C1qb

1427883_a_at procollagen, type III, alpha 1 -2.1 1.73E-02 juv Col3a1 1426762_s_at amine oxidase (flavin containing) domain 2 -2.1 4.3E-05 adult Aof2 1449072_a_at N-6 adenine-specific DNA methyltransferase 2 (putative) -2.1 2.8E-02 adult N6amt2 1449309_at cytochrome P450, family 8, subfamily b, polypeptide 1 -2.1 4.5E-03 adult Cyp8b1 1424521_at zinc finger, AN1 type domain 2B -2.1 2.5E-03 adult Zfand2b 1415807_s_at splicing factor, arginine/serine-rich 2 (SC-35) -2.1 3.0E-02 adult Sfrs2 1439144_at CWF19-like 1, cell cycle control (S. pombe) -2.1 1.9E-02 adult Cwf19l1 1449645_s_at chaperonin subunit 3 (gamma) -2.1 1.8E-03 adult Cct3 1452048_at mitochondrial ribosomal protein L12 -2.1 7.0E-03 adult Mrpl12 1436479_a_at dipeptidylpeptidase 7 -2.1 2.3E-03 adult Dpp7 1418702_a_at RIKEN cDNA 2810428I15 gene -2.1 5.0E-04 adult 2810428I15Rik 1437932_a_at claudin 1 -2.1 1.77E-02 juv Cldn1 1416521_at selenoprotein W, muscle 1 -2.1 6.6E-03 adult Sepw1

1428146_s_at acetyl-Coenzyme A acyltransferase 2 (mitochondrial 3-oxoacyl-Coenzyme A thiolase) -2.1 1.3E-08 adult Acaa2

1428196_a_at RIKEN cDNA 1200015F23 gene -2.1 6.7E-05 adult 1200015F23Rik 1416382_at cathepsin C -2.1 1.6E-05 adult Ctsc

1424921_at bromodomain containing 4 /// bone marrow stromal cell antigen 2 -2.1 4.3E-03 adult Brd4 /// Bst2

1423844_s_at cystathionine beta-synthase* -2.1 1.5E-04 adult Cbs 1460647_a_at nuclear receptor subfamily 2, group F, member 6 -2.1 1.5E-04 adult Nr2f6 1423119_at radial spokehead-like 2 -2.1 3.4E-02 adult Rshl2a 1417460_at interferon induced transmembrane protein 2 -2.1 2.6E-05 adult Ifitm2 1452754_at cysteine-rich with EGF-like domains 2 -2.2 2.24E-02 juv Creld2 1435290_x_at histocompatibility 2, class II antigen A, alpha -2.2 2.1E-02 adult H2-Aa 1417728_at methyl-CpG binding domain protein 3 -2.2 9.6E-04 adult Mbd3 1426710_at calmodulin 3 -2.2 1.4E-03 adult Calm3

1416102_at tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide -2.2 2.9E-02 adult Ywhaz

1420966_at solute carrier family 25 (mitochondrial carrier ornithine transporter), member 15 -2.2 1.7E-04 adult Slc25a15

1436884_x_at Ewing sarcoma breakpoint region 1 -2.2 3.0E-02 adult Ewsr1 1436012_s_at secernin 2 -2.2 6.0E-05 adult Scrn2 1418573_a_at hnRNP-associated with lethal yellow -2.2 3.2E-06 adult Raly 1428588_a_at mitochondrial ribosomal protein L41 -2.2 4.2E-03 adult Mrpl41 1437649_x_at peptidylprolyl isomerase B -2.2 2.6E-02 adult Ppib 1438009_at similar to histone 2a -2.2 1.2E-02 adult MGC73635 1421179_at tweety homolog 2 (Drosophila) -2.2 4.5E-06 adult Ttyh2 1416584_at mannosidase 2, alpha B2 -2.2 2.1E-05 adult Man2b2

1416874_a_at Paf1, RNA polymerase II associated factor, homolog (S. cerevisiae) -2.2 2.8E-05 adult Paf1

1417458_s_at CDC28 protein kinase regulatory subunit 2 -2.2 4.0E-03 adult Cks2 1424599_at fibrinogen-like protein 1 -2.3 2.8E-03 adult Fgl1 1417785_at phospholipase A1 member A -2.3 5.7E-05 adult Pla1a 1417870_x_at cathepsin Z* -2.3 1.5E-03 adult Ctsz 1420502_at spermidine/spermine N1-acetyl transferase 1 -2.3 1.5E-06 adult Sat1 1418932_at nuclear factor, interleukin 3, regulated -2.3 5.9E-06 both Nfil3

1424179_at pleckstrin homology domain containing, family J member 1 -2.3 4.5E-05 adult Plekhj1

1421915_a_at ST3 beta-galactoside alpha-2,3-sialyltransferase 3 -2.3 3.2E-03 adult St3gal3 1425895_a_at inhibitor of DNA binding 1 -2.3 5.6E-05 adult Id1 1449619_s_at Rho GTPase activating protein 9 -2.3 7.0E-04 adult Arhgap9 1415795_at spindlin -2.3 8.8E-04 adult Spin 1420476_a_at nucleosome assembly protein 1-like 1* -2.3 6.7E-04 adult Nap1l1 1451666_at ATP citrate lyase -2.3 1.6E-03 adult Acly 1430514_a_at CD99 antigen -2.3 1.4E-03 adult Cd99

1416567_s_at ATP synthase, H+ transporting, mitochondrial F1 complex, epsilon subunit -2.3 2.7E-03 adult Atp5e

1430519_a_at CCR4-NOT transcription complex, subunit 7 -2.3 7.2E-05 adult Cnot7

1416182_at amyloid beta (A4) precursor protein-binding, family A, member 3 -2.3 1.7E-05 adult Apba3

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1448169_at keratin 18 -2.3 1.9E-02 adult Krt18 1419095_a_at apolipoprotein M -2.3 1.6E-08 adult Apom

1455456_a_at translocase of inner mitochondrial membrane 50 homolog (yeast) -2.3 5.6E-08 adult Timm50

1425519_a_at CD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated) -2.3 1.4E-04 adult Cd74

1443696_s_at hyaluronic acid binding protein 2 -2.4 3.7E-06 adult Habp2 1451290_at microtubule-associated protein 1 light chain 3 alpha -2.4 1.3E-04 adult Map1lc3a 1456616_a_at basigin -2.4 1.6E-05 adult Bsg 1449046_a_at Josephin domain containing 2 -2.4 4.7E-06 adult Josd2 1416895_at ephrin A1* -2.4 6.5E-05 adult Efna1 1423166_at CD36 antigen -2.4 2.3E-08 adult Cd36 1423186_at T-cell lymphoma invasion and metastasis 2 -2.4 1.0E-03 adult Tiam2 1454373_x_at ubiquitin C -2.4 5.1E-05 adult Ubc

1439439_x_at eukaryotic translation elongation factor 1 delta (guanine nucleotide exchange protein) -2.5 2.2E-05 adult Eef1d

1418819_at ADP-ribosylation factor-like 8B -2.5 1.1E-08 adult Arl8b 1448262_at proteasome (prosome, macropain) subunit, beta type 2 -2.5 2.7E-08 adult Psmb2 1460684_at transmembrane 7 superfamily member 2 -2.5 9.5E-07 adult Tm7sf2 1449890_at UDP glucuronosyltransferase 2 family, polypeptide B37 -2.5 2.32E-02 juv Ugt2b37 1425589_at hydroxysteroid (17-beta) dehydrogenase 13 -2.5 1.1E-15 adult Hsd17b13 1450264_a_at choline kinase alpha -2.6 2.87E-02 juv Chka 1452000_s_at seryl-aminoacyl-tRNA synthetase 1 -2.6 2.5E-07 adult Sars 1434799_x_at aldolase 1, A isoform* -2.6 4.5E-07 adult Aldoa 1423078_a_at sterol-C4-methyl oxidase-like -2.6 2.6E-03 adult Sc4mol 1435193_at RIKEN cDNA A230050P20 gene -2.6 2.6E-08 adult A230050P20Rik 1416494_at NADH dehydrogenase (ubiquinone) Fe-S protein 5 -2.6 3.47E-02 juv Ndufs5 1423840_at coiled-coil domain containing 56 -2.6 9.7E-08 adult Ccdc56 1425099_a_at aryl hydrocarbon receptor nuclear translocator-like -2.6 3.69E-02 both Arntl 1417253_at FSHD region gene 1 -2.6 1.6E-08 adult Frg1 1424531_a_at transcription elongation factor A (SII), 3 -2.7 2.7E-03 adult Tcea3 1425108_a_at cDNA sequence BC004728 -2.7 3.5E-06 both BC004728

1420722_at elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 3 -2.8 3.71E-02 juv Elovl3

1424962_at transmembrane 4 superfamily member 4 -2.8 7.4E-11 adult Tm4sf4 1422537_a_at inhibitor of DNA binding 2 -2.8 1.1E-09 adult Id2 1449009_at T-cell specific GTPase -2.8 2.0E-12 adult Tgtp 1428062_at carboxypeptidase A1 -2.8 2.3E-06 adult Cpa1 1418760_at retinol dehydrogenase 11* -2.9 2.4E-11 adult Rdh11 1451721_a_at histocompatibility 2, class II antigen A, beta 1 (3 hits) -2.9 3.4E-09 adult H2-Ab1 1415993_at squalene epoxidase -2.9 1.2E-14 adult Sqle 1420515_a_at peptidoglycan recognition protein 2 -2.9 3.4E-09 adult Pglyrp2 1448300_at microsomal glutathione S-transferase 3 -2.9 1.8E-11 adult Mgst3 1419734_at actin, beta, cytoplasmic -3.0 7.7E-09 adult Actb

1424518_at RIKEN cDNA 2310016F22 gene /// cDNA sequence BC020489 -3.0 3.6E-04 adult 2310016F22Rik

1425927_a_at activating transcription factor 5 -3.0 2.4E-10 adult Atf5 1423397_at UDP glucuronosyltransferase 2 family, polypeptide B38 -3.0 3.86E-02 juv Ugt2b38 1426215_at dopa decarboxylase -3.1 8.1E-12 adult Ddc 1418490_at serine dehydratase-like -3.1 6.8E-15 adult Sdsl 1417273_at pyruvate dehydrogenase kinase, isoenzyme 4 -3.1 3.5E-22 adult Pdk4 1438322_x_at farnesyl diphosphate farnesyl transferase 1* -3.1 9.6E-12 adult Fdft1 1425869_a_at presenilin 2 -3.2 3.88E-02 juv Psen2 1433446_at 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1* -3.2 4.8E-11 adult Hmgcs1 1427893_a_at phosphomevalonate kinase -3.2 3.1E-13 adult Pmvk 1448898_at chemokine (C-C motif) ligand 9* -3.3 3.3E-11 adult Ccl9

1427347_s_at tubulin, beta 2a /// tubulin, beta 2b /// similar to tubulin, beta 3 -3.3 4.46E-02 juv Tubb2a /// Tubb2b

1416021_a_at fatty acid binding protein 5, epidermal* -3.3 3.6E-12 adult Fabp5 1448754_at retinol binding protein 1, cellular -3.3 1.2E-12 both Rbp1 1417705_at OTU domain, ubiquitin aldehyde binding 1 -3.4 2.1E-11 adult Otub1 1424022_at oxidative stress induced growth inhibitor 1 -3.4 1.5E-16 both Osgin1 1423418_at farnesyl diphosphate synthetase -3.6 3.8E-16 adult Fdps 1438855_x_at tumor necrosis factor, alpha-induced protein 2 -3.6 7.4E-22 adult Tnfaip2 1438676_at macrophage activation 2 like -3.8 7.0E-14 adult Mpa2l

1451457_at sterol-C5-desaturase (fungal ERG3, delta-5-desaturase) homolog (S. cerevisae) -3.8 9.5E-14 adult Sc5d

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1448986_x_at deoxyribonuclease II alpha -4.0 3.6E-26 adult Dnase2a

1417619_at growth arrest and DNA-damage-inducible, gamma interacting protein 1 -4.0 6.8E-22 adult Gadd45gip1

1451122_at isopentenyl-diphosphate delta isomerase* -4.3 1.0E-19 adult Idi1 1450646_at cytochrome P450, family 51* -4.3 6.8E-27 adult Cyp51

1428116_a_at dynein light chain Tctex-type 1 used to be :'t-complex testis expressed 1* -4.5 2.1E-23 adult Dynlt1

1438654_x_at monocyte to macrophage differentiation-associated 2* -4.5 1.2E-22 adult Mmd2

1450407_a_at acidic (leucine-rich) nuclear phosphoprotein 32 family, member A -4.6 4.59E-02 juv Anp32a

1448619_at 7-dehydrocholesterol reductase -4.6 1.4E-22 adult Dhcr7 1427981_a_at cysteine sulfinic acid decarboxylase -4.9 1.8E-34 adult Csad 1451675_a_at aminolevulinic acid synthase 2, erythroid -5.1 4.93E-02 both Alas2 1416055_at amylase 2, pancreatic -5.7 1.8E-19 adult Amy2 1417065_at early growth response 1 -6.0 2.5E-54 adult Egr1 gene expression levels for all the genes in this list were significantly elevated by at least 1.8 fold (LPE-test, S-PLUS). * multiple hits (data of the highest change are shown) FC - fold change

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Supplementary Table 2: Categories of changes in gene expression (Affymetrix GO)

GeneName Symbol regulation of transcription activating transcription factor 2 Atf2 activating transcription factor 5 Atf5 amine oxidase (flavin containing) domain 2 Aof2 aryl hydrocarbon receptor nuclear translocator-like Arntl basic helix-loop-helix domain containing, class B2 Bhlhb2 B-cell leukemia/lymphoma 6 Bcl6 BTB and CNC homology 2 Bach2 CCR4-NOT transcription complex, subunit 7 Cnot7 D site albumin promoter binding protein Dbp early growth response 1 Egr1 Ewing sarcoma breakpoint region 1 Ewsr1 GLI-Kruppel family member GLI2 Gli2 hepatic nuclear factor 4, alpha Hnf4a inhibitor of DNA binding 1 Id1 inhibitor of DNA binding 2 Id2 inhibitor of DNA binding 3 Id3 interferon activated gene 203 Ifi203 Kruppel-like factor 10 Klf10 methyl-CpG binding domain protein 3 Mbd3 nuclear factor, interleukin 3, regulated Nfil3 nuclear receptor interacting protein 1 Nrip1 nuclear receptor subfamily 1, group D, member 2 Nr1d2 nuclear receptor subfamily 2, group F, member 6 Nr2f6 oxidative stress induced growth inhibitor 1 Osgin1 period homolog 3 (Drosophila) Per3 signal transducer and activator of transcription 1 Stat1 splicing factor proline/glutamine rich (polypyrimidine tract binding protein associated) Sfpq splicing factor, arginine/serine-rich 2 (SC-35) Sfrs2 TAR (HIV) RNA binding protein 2 Tarbp2 thyrotroph embryonic factor Tef trans-acting transcription factor 1 Sp1 transcription elongation factor A (SII), 3 Tcea3 TSC22 domain family 3 Tsc22d3 v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B (avian) Mafb regulation of protein synthesis ADP-ribosylation factor-like 8B Arl8b CUG triplet repeat, RNA binding protein 2 Cugbp2 eukaryotic translation elongation factor 1 delta (guanine nucleotide exchange protein) Eef1d eukaryotic translation initiation factor 4E binding protein 2 Eif4ebp2 FSHD region gene 1 Frg1 MAP kinase-interacting serine/threonine kinase 2 Mknk2 mitochondrial ribosomal protein L12 Mrpl12 mitochondrial ribosomal protein L41 Mrpl41 pumilio 1 (Drosophila) Pum1 seryl-aminoacyl-tRNA synthetase Sars threonyl-tRNA synthetase Tars protein and aminoacid phosphorylation events bromodomain containing 4 /// bone marrow stromal cell antigen 2 Brd4 /// Bst2 expressed sequence AW548124 AW548124 heat shock protein 8 Hspb8 MAP kinase-interacting serine/threonine kinase 2 Mknk2 phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha) Pik3r1 Protein tyrosine phosphatase 4a2 Ptp4a2 proviral integration site 3 Pim3 pyruvate dehydrogenase kinase, isoenzyme 4 Pdk4 serine/threonine kinase 25 (yeast) Stk25 SH3-binding kinase 1 Sbk1 translocase of inner mitochondrial membrane 50 homolog (yeast) Timm50 wee 1 homolog (S. pombe) Wee1

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proteolysis carboxypeptidase A1 Cpa1 cathepsin C Ctsc cathepsin Z Ctsz cytochrome P450, family 51 Cyp51 dipeptidylpeptidase 7 Dpp7 hyaluronic acid binding protein 2 Habp2 presenilin 2 Psen2 secernin 2 Scrn2 ubiquitin-dependent processes, protein modification homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1 Herpud1 microtubule-associated protein 1 light chain 3 alpha Map1lc3a neural precursor cell expressed, developmentally down-regulated gene 4-like Nedd4l OTU domain, ubiquitin aldehyde binding 1 Otub1 proteasome (prosome, macropain) subunit, beta type 2 Psmb2 ST3 beta-galactoside alpha-2,3-sialyltransferase 3 St3gal3 STIP1 homology and U-Box containing protein 1 Stub1 ubiquitin C Ubc Ubiquitin specific peptidase 14 Usp14 ubiquitin specific peptidase 2 Usp2 protein folding caseinolytic peptidase X (E.coli) Clpx CD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated) Cd74 chaperonin subunit 3 (gamma) Cct3 heat shock protein 8 Hspb8 peptidylprolyl isomerase B Ppib peptidylprolyl isomerase F (cyclophilin F) Ppif STIP1 homology and U-Box containing protein 1 Stub1 carbohydrate metabolism 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 Pfkfb3 aldolase 1, A isoform Aldoa amylase 2, pancreatic Amy2 ATP citrate lyase Acly fatty acid binding protein 5, epidermal Fabp5 glycogen synthase 2 /// similar to glycogen synthase 2 Gys2 mannosidase 2, alpha B2 Man2b2 phosphoenolpyruvate carboxykinase 1, cytosolic Pck1 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 Slc7a2 lipid/steroid/sterol biosynthesis and metabolism 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 Hmgcs1 7-dehydrocholesterol reductase Dhcr7 acetyl-Coenzyme A acyltransferase 2 (mitochondrial 3-oxoacyl-Coenzyme A thiolase) Acaa2 acyl-CoA synthetase long-chain family member 1 Acsl1 ATP citrate lyase Acly beta-1,4-N-acetyl-galactosaminyl transferase 1 B4galnt1 CD36 antigen Cd36 choline kinase alpha Chka cytochrome P450, family 51 Cyp51 elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 3 Elovl3 farnesyl diphosphate farnesyl transferase 1 Fdft1 farnesyl diphosphate synthetase Fdps fatty acid binding protein 5, epidermal Fabp5 hepatic nuclear factor 4, alpha Hnf4a hydroxysteroid (17-beta) dehydrogenase 11 Hsd17b11 hydroxysteroid (17-beta) dehydrogenase 13 Hsd17b13 isopentenyl-diphosphate delta isomerase Idi1 lipin 1 Lpin1 lysophosphatidylglycerol acyltransferase 1 Lpgat1 phosphatidic acid phosphatase type 2B Ppap2b phosphatidylcholine transfer protein Pctp phosphoenolpyruvate carboxykinase 1, cytosolic Pck1 phospholipase A1 member A Pla1a phosphomevalonate kinase Pmvk

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RIKEN cDNA 2310016F22 gene 2310016F22Rik sterol-C4-methyl oxidase-like Sc4mol sterol-C5-desaturase (fungal ERG3, delta-5-desaturase) homolog (S. cerevisae) Sc5d transmembrane 7 superfamily member 2 Tm7sf2 biosynthesis/metabolsim, other adenylate kinase 3 alpha-like 1 Ak3l1 aminolevulinic acid synthase 1 Alas1 aminolevulinic acid synthase 2, erythroid Alas2 coproporphyrinogen oxidase Cpox cystathionine beta-synthase Cbs cysteine sulfinic acid decarboxylase Csad cytochrome P450, family 3, subfamily a, polypeptide 13 Cyp3a13 deiodinase, iodothyronine, type I Dio1 dopa decarboxylase Ddc folylpolyglutamyl synthetase Fpgs hydroxysteroid (17-beta) dehydrogenase 13 Hsd17b13 nucleosome assembly protein 1-like 1 Nap1l1 retinol dehydrogenase 11 Rdh11 serine dehydratase-like Sdsl squalene epoxidase Sqle threonyl-tRNA synthetase Tars UDP glucuronosyltransferase 2 family, polypeptide B37 Ugt2b37 UDP glucuronosyltransferase 2 family, polypeptide B38 Ugt2b38 electron transport amine oxidase (flavin containing) domain 2 Aof2 aminolevulinic acid synthase 2, erythroid Alas2 cytochrome P450, family 2, subfamily c, polypeptide 50 /// cytochrome P450 Cyp2c50 /// Cyp2c54 cytochrome P450, family 2, subfamily g, polypeptide 1 Cyp2g1 cytochrome P450, family 2. subfamily c, polypeptide 37 /// cytochrome P450, family 2, subfamily c, polypeptide 50 /// cytochrome P450 /// similar to cytochrome P450 Cyp2c37 /// Cyp2c50 /// Cyp2c54 /// LOC639023 cytochrome P450, family 3, subfamily a, polypeptide 13 Cyp3a13 cytochrome P450, family 51 Cyp51 cytochrome P450, family 8, subfamily b, polypeptide 1 Cyp8b1 squalene epoxidase Sqle threonyl-tRNA synthetase Tars zinc finger protein 106 Zfp106 transport, other amyloid beta (A4) precursor protein-binding, family A, member 3 Apba3 apolipoprotein M Apom ATP synthase, H+ transporting, mitochondrial F1 complex, epsilon subunit Atp5e caseinolytic peptidase X (E.coli) Clpx CD36 antigen Cd36 lipocalin 13 Lcn13 phosphatidylcholine transfer protein Pctp polycystic kidney disease 2 Pkd2 potassium channel, subfamily K, member 5 Kcnk5 procollagen, type III, alpha 1 Col3a1 radial spokehead-like 2A Rshl2a retinol binding protein 1, cellular Rbp1 RIKEN cDNA 2510005D08 gene 2510005D08Rik solute carrier family 20, member 1 Slc20a1 solute carrier family 25 (mitochondrial carrier ornithine transporter), member 15 Slc25a15 solute carrier family 4 (anion exchanger), member 4 Slc4a4 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 Slc7a2 synaptophysin-like protein Sypl T-cell lymphoma invasion and metastasis 2 Tiam2 translocase of inner mitochondrial membrane 50 homolog (yeast) Timm50 cell cycle, proliferation and differentiation/cell fate 7-dehydrocholesterol reductase Dhcr7 activating transcription factor 5 Atf5 aryl hydrocarbon receptor nuclear translocator-like Arntl B-cell leukemia/lymphoma 6 Bcl6 bone morphogenetic protein 2 Bmp2 calmodulin 3 Calm3 CD74 antigen (invariant polypeptide of major histocompatibility complex, class II

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antigen-associated) Cd74 CDC28 protein kinase regulatory subunit 2 Cks2 connective tissue growth factor Ctgf deoxyribonuclease II alpha Dnase2a DNA cross-link repair 1A, PSO2 homolog (S. cerevisiae) Dclre1a early growth response 1 Egr1 GLI-Kruppel family member GLI2 Gli2 growth arrest and DNA-damage-inducible, gamma interacting protein 1 Gadd45gip1 inhibitor of DNA binding 1 Id1 inhibitor of DNA binding 2 Id2 inhibitor of DNA binding 3 Id3 Kruppel-like factor 10 Klf10 leukocyte cell derived chemotaxin 1 Lect1 methyl-CpG binding domain protein 3 Mbd3 microtubule-associated protein, RP/EB family, member 2 Mapre2 monocyte to macrophage differentiation-associated 2 Mmd2 neuropilin 1 Nrp1 nuclear receptor interacting protein 1 Nrip1 nuclear receptor subfamily 2, group F, member 6 Nr2f6 period homolog 3 (Drosophila) Per3 phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha) Pik3r1 polycystic kidney disease 2 Pkd2 presenilin 2 Psen2 selenoprotein W, muscle 1 Sepw1 sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3E Sema3e spindlin Spin tissue inhibitor of metalloproteinase 2 Timp2 tumor necrosis factor, alpha-induced protein 2 Tnfaip2 wee 1 homolog (S. pombe) Wee1 circadian rhythm aryl hydrocarbon receptor nuclear translocator-like Arntl CCR4 carbon catabolite repression 4-like (S. cerevisiae) Ccrn4l D site albumin promoter binding protein Dbp nuclear receptor subfamily 2, group F, member 6 Nr2f6 period homolog 3 (Drosophila) Per3 signal transduction arginine vasopressin receptor 1A Avpr1a aryl hydrocarbon receptor nuclear translocator-like Arntl chemokine (C-C motif) ligand 9 Ccl9 GLI-Kruppel family member GLI2 Gli2 interleukin 6 receptor, alpha Il6ra metallothionein 2 Mt2 period homolog 3 (Drosophila) Per3 regulator of G-protein signaling 16 Rgs16 regulator of G-protein signaling 5 Rgs5 Rho GTPase activating protein 9 Arhgap9 T-cell lymphoma invasion and metastasis 2 Tiam2 signal transducer and activator of transcription 1 Stat1 signaling calmodulin 3 Calm3 connective tissue growth factor Ctgf early growth response 1 Egr1 ephrin A1 Efna1 ERBB receptor feedback inhibitor 1 Errfi1 eukaryotic translation initiation factor 4E binding protein 2 Eif4ebp2 phosphatidic acid phosphatase type 2B Ppap2b phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha) Pik3r1 presenilin 2 Psen2 regulator of G-protein signaling 16 Rgs16 regulator of G-protein signaling 5 Rgs5 signal transducer and activator of transcription 1 Stat1 zinc finger protein 106 Zfp106 immune response CD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated) Cd74 chemokine (C-C motif) ligand 9 Ccl9

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complement component 1, q subcomponent, beta polypeptide C1qb early growth response 1 Egr1 histocompatibility 2, class II antigen A, alpha H2-Aa histocompatibility 2, class II antigen A, alpha /// histocompatibility 2, class II antigen E alpha H2-Aa /// H2-Ea histocompatibility 2, class II antigen A, beta 1 H2-Ab1 interferon activated gene 203 Ifi203 interferon induced transmembrane protein 2 Ifitm2 macrophage activation 2 like /// similar to macrophage activation 2 like /// similar to macrophage activation 2 like Mpa2l OTU domain, ubiquitin aldehyde binding 1 Otub1 peptidoglycan recognition protein 2 Pglyrp2 TAP binding protein Tapbp TAP binding protein Tapbp T-cell specific GTPase Tgtp regulation of apoptosis activating transcription factor 5 Atf5 B-cell leukemia/lymphoma 6 Bcl6 CD36 antigen Cd36 CD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated) Cd74 cell adhesion claudin 1 Cldn1 deoxyribonuclease II alpha Dnase2a epithelial V-like antigen 1 Eva1 procollagen, type III, alpha 1 Col3a1 TSC22 domain family 3 Tsc22d3 cytoskeleton, microtubuli coronin, actin binding protein, 2B Coro2b dynein light chain Tctex-type 1 Dynlt1 keratin 18 Krt18 kinesin family member 1B Kif1b tubulin, beta 2a /// tubulin, beta 2b /// similar to tubulin, beta 3 Tubb2a /// Tubb2b

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Supplementary Table 3: Selected genes upregulated in expression during response to accumulation of mutant ATZ

GeneName FC juv

Adjusted p-Value

juv QPCR

FC ad

Adjusted p-Value

adult QPCR

Gene Symbol

D site albumin promoter binding protein (2 hits) 9.1 0.0E+00 N.D. 4.1 0.00E+00 N.D. Dbp phosphatidylcholine transfer protein (2 hits) 6.0 0.0E+00 N.D. N.S. N.S. N.D. Pctp CCR4 carbon catabolite repression 4-like (S. cerevisiae) 5.9 0.00E+00 N.D. 9.6 0.00E+00 N.D. Ccrn4l

ubiquitin specific protease 2 (2 hits) 4.6 0.0E+00 conf 4.3 0.0E+00 N.D. Usp2 period homolog 3 (Drosophila) 3.0 1.7E-38 N.D. 2.1 2.6E-04 N.D. Per3 protein tyrosine phosphatase 4a2 3.0 3.6E-20 N.C. N.S. N.S. N.D. Ptp4a2 deiodinase, iodothyronine, type I 2.7 1.66E-13 N.D. 2.7 7.03E-11 N.D. Dio1 lipocalin 13 2.5 1.00E-11 N.D. N.S. N.S. N.D. Lcn13 cytochrome P450, family 2, subfamily a, polypeptide 4-5 2.4 2.51E-11 N.D. N.S. N.S. N.D. Cyp2a4 ///

Cyp2a5 DNA cross-link repair 1A, PSO2 homolog (S. cerevisiae) 2.2 3.01E-11 N.D. 2.6 1.1E-04 N.D. Dclre1a

thyrotroph embryonic factor 2.1 1.53E-09 N.D. 2.0 4.2E-05 N.D. Tef interferon activated gene 203 (2 hits) 2.1 4.8E-09 conf N.S. N.S. N.D. Ifi203 metallothionein 2 2.1 1.4E-08 N.D. N.S. N.S. N.D. Mt2 TAR (HIV) RNA binding protein 2 2.0 3.2E-08 conf N.S. N.S. N.D. Tarbp2 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 1.9 3.40E-07 N.D. 2.2 1.4E-06 N.D. Slc7a2

leukocyte cell derived chemotaxin 1 1.9 4.84E-06 N.D. N.S. N.S. N.D. Lect1 cytochrome P450, family 2, subfamily g, polypeptide1 1.8 6.17E-06 N.D. N.S. N.S. N.D. Cyp2g1 B-cell leukemia/lymphoma 6 1.8 7.8E-06 conf N.S. N.S. N.D. Bcl6 regulator of G-protein signaling 16 1.8 9.7E-06 conf 5.4 0.0E+00 conf Rgs16 6phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 1.8 1.4E-05 N.D. 2.1 8.09E-03 N.D. Pfkfb3 lipin 1 (2 hits) N.S. N.S. N.D. 6.4 0.00E+00 N.D. Lpin1 cytochrome P450, family 2, subfamily c, polypeptide 50 /// cytochrome P450 (2 hits) N.S. N.S. N.D. 5.6 5.02E-12 conf Cyp2c50

aminolevulinic acid synthase 1 N.S. N.S. N.D. 4.0 0 N.D. Alas1 lipin 2 (2 hits) N.S. N.S. N.D. 3.0 1.2E-10 N.D. Lpin2 peptidylprolyl isomerase F (cyclophilin F) N.S. N.S. N.D. 2.8 1.73E-14 0.0 Ppif phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha) N.S. N.S. N.D. 2.7 2.51E-11 conf Pik3r1

Kruppel-like factor 10 N.S. N.S. N.D. 2.7 0.00E+00 N.D. Klf10 regulator of G-protein signaling 5 N.S. N.S. N.D. 2.6 6.58E-06 conf Rgs5 activating transcription factor 2 N.S. N.S. N.D. 2.6 1.71E-05 N.D. Atf2 interleukin 6 receptor, alpha N.S. N.S. N.D. 2.6 1.80E-03 N.D. Il6ra tissue inhibitor of metalloproteinase 2 N.S. N.S. N.D. 2.6 4.54E-04 N.D. Timp2 ataxin 10 N.S. N.S. N.D. 2.6 2.85E-10 N.D. Atxn10 nuclear receptor interacting protein 1 N.S. N.S. N.D. 2.5 4.6E-07 conf Nrip1 proviral integration site 3 N.S. N.S. N.D. 2.4 1.8E-06 N.D. Pim3 trans-acting transcription factor 1 N.S. N.S. N.D. 2.4 1.89E-03 N.D. Sp1 homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1 N.S. N.S. N.D. 2.4 1.28E-05 N.D. Herpud1

zinc finger protein 106 N.S. N.S. N.D. 2.3 1.71E-04 N.D. Zfp106 Similar to membrane metallo endopeptidase N.S. N.S. N.D. 2.3 8.75E-03 conf --- serum deprivation response N.S. N.S. N.D. 2.3 3.65E-04 N.D. Sdpr hepatic nuclear factor 4, alpha N.S. N.S. N.D. 2.2 1.05E-02 N.D. Hnf4a connective tissue growth factor N.S. N.S. N.D. 2.2 1.62E-09 N.D. Ctgf eukaryotic translation initiation factor 4E binding protein 2 N.S. N.S. N.D. 2.2 4.35E-02 N.D. Eif4ebp2

polycystic kidney disease 2 N.S. N.S. N.D. 2.2 8.45E-03 conf Pkd2 ubiquitin specific protease 14 N.S. N.S. N.D. 2.1 3.04E-07 N.D. Usp14 NS, not significant; ND, not done; FC, fold change; juv, juvenile; conf, confirmed. Changes in gene expression that were confirmed by real time QPCR are shown in bold. For changes in gene expression that were identified by multiple hits, the change of the greatest magnitude is reported.

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Supplementary Table 4: Selected genes downregulated in expression during response to accumulation of mutant ATZ GeneName FC

juv Adjusted p-Value

juv QPCR

FC adult

Adjusted p-Value

adult QPCR

Gene Symbol

aminolevulinic acid synthase 2, erythroid -5.1 4.9E-02 N.D. -2.5 5.5E-17 N.D. Alas2 presenilin 2 -3.2 3.9E-02 conf N.S. N.S. N.D. Psen2 UDP glucuronosyltransferase 2 family, polypeptide B38 -3.0 3.9E-02 N.D. N.S. N.S. N.D. Ugt2b38

Oxidative stress induced growth inhibitor -3.0 3.8E-02 N.D. -3.4 1.5E-16 N.D. Osgin1 elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 3 -2.8 3.7E-02 N.D. N.S. N.S. N.D. Elovl3

aryl hydrocarbon receptor nuclear translocator-like -2.6 3.69E-02 N.D. -2.3 4.9E-10 N.D. Arntl choline kinase alpha -2.6 2.9E-02 N.D. N.S. N.S. N.D. Chka retinol binding protein 1, cellular -2.1 1.9E-02 N.D. -3.3 1.2E-12 N.C. Rbp1 procollagen, type III, alpha 1 -2.1 1.7E-02 conf N.S. N.S. N.D. Col3a1 suppression of tumorigenicity 5 -2.0 1.5E-02 N.D. N.S. N.S. N.D. St5 inhibitor of DNA binding 3 -1.9 1.3E-02 conf N.S. N.S. N.D. Id3 nuclear factor, interleukin 3, regulated -1.9 1.13E-02 N.D. -2.3 5.9E-06 N.D. Nfil3 arginine vasopressin receptor 1A -1.8 1.0E-02 N.D. -2.0 6.36E-05 N.D. Avpr1a cDNA sequence BC004728 -1.8 5.81E-03 N.D. -2.7 3.5E-06 N.D. BC004728 early growth response 1 N.S. N.S. N.D. -6.0 2.53E-54 N.D. Egr1 monocyte to macrophage differentiation-associated 2 (2 hits) N.S. N.S. N.D. -4.5 1.23E-22 N.D. Mmd2

dynein light chain Tctex-type 1 used to be :'t-complex testis expressed 1 (2 hits) N.S. N.S. N.D. -4.5 2.15E-23 N.C. Dynlt1

cytochrome P450, 51 (2 hits) N.S. N.S. N.D. -4.3 6.80E-27 conf Cyp51 sterol-C5-desaturase (fungal ERG3, delta-5-desaturase) homolog (S. cerevisae) N.S. N.S. N.D. -3.8 9.46E-14 N.C. Sc5d

tumor necrosis factor, alpha-induced protein 2 N.S. 0.07+ N.D. -3.6 7.4E-22 N.D. Tnfaip2 fatty acid binding protein 5, epidermal (2 hits) N.S. 0.05+ N.D. -3.3 3.57E-12 conf Fabp5 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (4 hits) N.S. N.S. N.D. -3.2 4.84E-11 N.D. Hmgcs1

farnesyl diphosphate farnesyl transferase 1 (2 hits) N.S. N.S. N.D. -3.1 9.56E-12 N.D. Fdft1 farnesyl diphosphate synthetase N.S. N.S. N.D. -3.1 9.56E-12 N.C. Fdps activating transcription factor 5 N.S. N.S. N.D. -3.0 2.4E-10 N.D. Atf5 squalene epoxidase N.S. N.S. N.D. -2.9 1.17E-14 conf Sqle T-cell specific GTPase N.S. N.S. N.D. -2.8 1.99E-12 N.C. Tgtp sterol-C4-methyl oxidase-like N.S. N.S. N.D. -2.6 2.6E-03 N.C. Sc4mol proteasome (prosome, macropain) subunit, beta type 2 N.S. N.S. N.D. -2.5 1.20E-12 N.D. Psmb2 CD36 antigen N.S. 0.01+ N.D. -2.4 2.3E-08 N.D. Cd36 CCR4-NOT transcription complex, subunit 7 N.S. N.S. N.D. -2.3 3.19E-09 N.D. Cnot7 spindlin N.S. N.S. N.D. -2.3 8.79E-04 N.D. Spin cathepsin Z (2 hits) N.S. N.S. N.D. -2.3 1.54E-03 N.D. Ctsz phospholipase A1 member A N.S. N.S. N.D. -2.3 5.69E-05 N.C. Pla1a TAP binding protein (2 hits) N.S. N.S. N.D. -2.2 2.78E-09 N.D. Tapbp mannosidase 2, alpha B2 N.S. N.S. N.D. -2.2 9.27E-10 N.D. Man2b2 peptidylprolyl isomerase B N.S. N.S. N.D. -2.2 1.14E-06 N.D. Ppib cathepsin C N.S. N.S. N.D. -2.1 1.58E-05 N.D. Ctsc acetyl-Coenzyme A acyltransferase 2 (mitochondrial 3-oxoacyl-Coenzyme A thiolase) N.S. N.S. N.D. -2.1 1.33E-08 N.D. Acaa2

cytochrome P450, family 8, subfamily b, polypeptide1 N.S. N.S. N.D. -2.1 1.98E-07 N.D. Cyp8b1 COP9 (constitutive photomorphogenic) homolog, subunit 6 (Arabidopsis thaliana) N.S. N.S. N.D. -2.0 2.7E-02 N.C. Cops6

signal transducer and activator of transcription 1 N.S. N.S. N.D. -2.0 9.37E-07 N.D. Stat1 histocompatibility 2, class II antigen E alpha N.S. N.S. N.D. -2.0 2.1E-06 N.D. H2-Aa NS, not significant; ND, not done; FC, fold change; juv, juvenile; conf, confirmed. Changes in gene expression that were confirmed by real time QPCR are shown in bold. For changes in gene expression that were identified by multiple hits, the change of the greatest magnitude is reported.

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