JAX Liver HF Affy M430 2.0 (Jul11) MDP

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High-fat diets are associated with increased obesity and metabolic disease in mice and humans. Here we used analysis of variance (ANOVA) to scrutinize a microarray data set consisting of 10 inbred strains of mice from both sexes fed atherogenic high-fat and control chow diets. An overall F-test was applied to the 40 unique groups of strain-diet-sex to identify 15,288 genes with altered transcription. Bootstrapping k-means clustering separated these changes into four strain-dependent expression patterns, including two sex-related profiles and two diet-related profiles. Sex-induced effects correspond to secretion (males) or fat and energy metabolism (females), whereas diet-induced changes relate to neurological processes (chow) or immune response (high-fat). The full set of pairwise contrasts for differences between strains within sex (90 different statistical tests) uncovered 32,379 total changes. These differences were unevenly distributed across strains and between sexes, indicating that strain-specific responses to high-fat diet differ between sexes. Correlations between expression levels and 8 obesity-related traits identified 5,274 associations between transcript abundance and measured phenotypic endpoints. From this number, 2,678 genes are positively correlated with total cholesterol levels and associate with immune-related categories while 2,596 genes are negatively correlated with cholesterol and connect to cholesterol synthesis. Keywords: gene expression analysis, strain comparision, effect of dietary fat, sex-specific effects

Experiment design

Expression profiling by array.

One group of mice was fed an atherogenic high-fat (30% fat) diet containing cholic acid to increase fat uptake and another was fed a low-fat (6% fat) regular chow diet. Males and females from both diets were studied for mouse strains 129S1/SvImJ, A/J, BALB/cJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, I/LnJ, MRL/MpJ-Tnfrsf6lpr/J, NZB/BINJ, PERA/Ei, and SM/J. All strains were sacrificed between 11- and 13 weeks of age except for CAST and PERA, which were harvested after 50 weeks of age. CAST and PERA were subsequently removed from our analysis based on discrepant harvest age, but can be found in our database (see below). Three replicate animals were used for each combination of diet, strain, and sex, resulting in a total of 120 mice surveyed for gene expression.

About cases

Index Sample ID Strain ID HF=high-fat (30% fat)
6C=low-fat (6% fat)
Replicate Animal
1 GSM264767 129S1/SvImJ 6C Rep1
2 GSM264768 129S1/SvImJ 6C Rep2
3 GSM264769 129S1/SvImJ 6C Rep3
4 GSM264770 129S1/SvImJ HF Rep1
5 GSM264771 129S1/SvImJ HF Rep2
6 GSM264772 129S1/SvImJ HF Rep3
7 GSM264773 129S1/SvImJ 6C Rep1
8 GSM264774 129S1/SvImJ 6C Rep2
9 GSM264775 129S1/SvImJ 6C Rep3
10 GSM264776 129S1/SvImJ HF Rep1
11 GSM264777 129S1/SvImJ HF Rep2
12 GSM264778 129S1/SvImJ HF Rep3
13 GSM264779 A/J 6C Rep1
14 GSM264780 A/J 6C Rep2
15 GSM264781 A/J 6C Rep3
16 GSM264782 A/J HF Rep1
17 GSM264783 A/J HF Rep2
18 GSM264784 A/J HF Rep3
19 GSM264785 A/J 6C Rep1
20 GSM264786 A/J 6C Rep2
21 GSM264787 A/J 6C Rep3
22 GSM264788 A/J HF Rep1
23 GSM264789 A/J HF Rep2
24 GSM264790 A/J HF Rep3
25 GSM264791 C57BL/6J 6C Rep1
26 GSM264792 C57BL/6J 6C Rep2
27 GSM264793 C57BL/6J 6C Rep3
28 GSM264794 C57BL/6J HF Rep1
29 GSM264795 C57BL/6J HF Rep2
30 GSM264796 C57BL/6J HF Rep3
31 GSM264797 C57BL/6J 6C Rep1
32 GSM264798 C57BL/6J 6C Rep2
33 GSM264799 C57BL/6J 6C Rep3
34 GSM264800 C57BL/6J HF Rep1
35 GSM264801 C57BL/6J HF Rep2
36 GSM264802 C57BL/6J HF Rep3
37 GSM264803 BALB/cJ 6C Rep1
38 GSM264804 BALB/cJ 6C Rep2
39 GSM264805 BALB/cJ 6C Rep3
40 GSM264806 BALB/cJ HF Rep1
41 GSM264807 BALB/cJ HF Rep2
42 GSM264808 BALB/cJ HF Rep3
43 GSM264809 BALB/cJ 6C Rep1
44 GSM264810 BALB/cJ 6C Rep2
45 GSM264811 BALB/cJ 6C Rep3
46 GSM264813 BALB/cJ HF Rep1
47 GSM264814 BALB/cJ HF Rep2
48 GSM264815 BALB/cJ HF Rep3
49 GSM264845 C3H/HeJ 6C Rep1
50 GSM264846 C3H/HeJ 6C Rep2
51 GSM264847 C3H/HeJ 6C Rep3
52 GSM264848 C3H/HeJ HF Rep1
53 GSM264849 C3H/HeJ HF Rep2
54 GSM264850 C3H/HeJ HF Rep3
55 GSM264852 C3H/HeJ 6C Rep1
56 GSM264853 C3H/HeJ 6C Rep2
57 GSM264855 C3H/HeJ 6C Rep3
58 GSM264856 C3H/HeJ HF Rep1
59 GSM264857 C3H/HeJ HF Rep2
60 GSM264858 C3H/HeJ HF Rep3
61 GSM264859 CAST/EiJ 6C Rep1
62 GSM264861 CAST/EiJ 6C Rep2
63 GSM264862 CAST/EiJ 6C Rep3
64 GSM264863 CAST/EiJ HF Rep1
65 GSM264864 CAST/EiJ HF Rep2
66 GSM264865 CAST/EiJ HF Rep3
67 GSM264866 CAST/EiJ 6C Rep1
68 GSM264867 CAST/EiJ 6C Rep2
69 GSM264868 CAST/EiJ 6C Rep3
70 GSM264869 CAST/EiJ HF Rep1
71 GSM264870 CAST/EiJ HF Rep2
72 GSM264871 CAST/EiJ HF Rep3
73 GSM264872 DBA/2J 6C Rep1
74 GSM264873 DBA/2J 6C Rep2
75 GSM264874 DBA/2J 6C Rep3
76 GSM264875 DBA/2J HF Rep1
77 GSM264876 DBA/2J HF Rep2
78 GSM264877 DBA/2J HF Rep3
79 GSM264890 DBA/2J 6C Rep1
80 GSM264891 DBA/2J 6C Rep2
81 GSM264892 DBA/2J 6C Rep3
82 GSM264893 DBA/2J HF Rep1
83 GSM264894 DBA/2J HF Rep2
84 GSM264895 DBA/2J HF Rep3
85 GSM264896 I/LnJ 6C Rep1
86 GSM264897 I/LnJ 6C Rep2
87 GSM264898 I/LnJ 6C Rep3
88 GSM264899 I/LnJ HF Rep1
89 GSM264900 I/LnJ HF Rep2
90 GSM264901 I/LnJ HF Rep3
91 GSM264902 I/LnJ 6C Rep1
92 GSM264903 I/LnJ 6C Rep2
93 GSM264904 I/LnJ 6C Rep3
94 GSM264905 I/LnJ HF Rep1
95 GSM264906 I/LnJ HF Rep2
96 GSM264907 I/LnJ HF Rep3
97 GSM264908 MRL/MpJ-Fas/J 6C Rep1
98 GSM264909 MRL/MpJ-Fas/J 6C Rep2
99 GSM264910 MRL/MpJ-Fas/J 6C Rep3
100 GSM264912 MRL/MpJ-Fas/J HF Rep1
101 GSM264913 MRL/MpJ-Fas/J HF Rep2
102 GSM264914 MRL/MpJ-Fas/J HF Rep3
103 GSM264915 MRL/MpJ-Fas/J 6C Rep1
104 GSM264916 MRL/MpJ-Fas/J 6C Rep2
105 GSM264917 MRL/MpJ-Fas/J 6C Rep3
106 GSM264918 MRL/MpJ-Fas/J HF Rep1
107 GSM264920 MRL/MpJ-Fas/J HF Rep2
108 GSM264921 MRL/MpJ-Fas/J HF Rep3
109 GSM264922 NZB/BlNJ 6C Rep1
110 GSM264924 NZB/BlNJ 6C Rep2
111 GSM264925 NZB/BlNJ 6C Rep3
112 GSM264926 NZB/BlNJ HF Rep1
113 GSM264928 NZB/BlNJ HF Rep2
114 GSM264929 NZB/BlNJ HF Rep3
115 GSM264930 NZB/BlNJ 6C Rep1
116 GSM264931 NZB/BlNJ 6C Rep2
117 GSM264932 NZB/BlNJ 6C Rep3
118 GSM264933 NZB/BlNJ HF Rep1
119 GSM264935 NZB/BlNJ HF Rep2
120 GSM264936 NZB/BlNJ HF Rep3
121 GSM265061 PERA/EiJ 6C Rep1
122 GSM265062 PERA/EiJ 6C Rep2
123 GSM265063 PERA/EiJ 6C Rep3
124 GSM265064 PERA/EiJ HF Rep1
125 GSM265065 PERA/EiJ HF Rep2
126 GSM265066 PERA/EiJ HF Rep3
127 GSM265067 PERA/EiJ 6C Rep1
128 GSM265068 PERA/EiJ 6C Rep2
129 GSM265069 PERA/EiJ 6C Rep3
130 GSM265070 PERA/EiJ HF Rep1
131 GSM265071 PERA/EiJ HF Rep2
132 GSM265072 PERA/EiJ HF Rep3
133 GSM265074 SM/J 6C Rep1
134 GSM265075 SM/J 6C Rep2
135 GSM265105 SM/J 6C Rep3
136 GSM265217 SM/J HF Rep1
137 GSM265248 SM/J HF Rep2
138 GSM265275 SM/J HF Rep3
139 GSM265324 SM/J 6C Rep1
140 GSM265331 SM/J 6C Rep2
141 GSM265357 SM/J 6C Rep3
142 GSM265358 SM/J HF Rep1
143 GSM265359 SM/J HF Rep2
144 GSM265360 SM/J HF Rep3

About tissue


About platform

[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array. Affymetrix submissions are typically submitted to GEO using the GEOarchive method described at http://www.ncbi.nlm.nih.gov/projects/geo/info/geo_affy.html All probe sets represented on the GeneChip Mouse Expression Set 430 are included on the GeneChip Mouse Genome 430 2.0 Array. The sequences from which these probe sets were derived were selected from GenBank«, dbEST, and RefSeq. The sequence clusters were created from the UniGene database (Build 107, June 2002) and then refined by analysis and comparison with the publicly available draft assembly of the mouse genome from the Whitehead Institute for Genome Research (MGSC, April 2002).


Churchill GA, Paigen B, Shockley KR, Witmer D


Burgess-Herbert SL, Cox A, Tsaih SW, Paigen B. Practical applications of the bioinformatics toolbox for narrowing quantitative trait loci. Genetics 2008 Dec;180(4):2227-35. PMID: 18845850 Shockley KR, Witmer D, Burgess-Herbert SL, Paigen B et al. Effects of atherogenic diet on hepatic gene expression across mouse strains. Physiol Genomics 2009 Nov 6;39(3):172-82. PMID: 19671657


Churchill GA, Paigen B, Shockley KR, Witmer D