Microarray analysis of insulin-regulated gene expression in the liver: the use of transgenic mice co-expressing insulin-siRNA and human IDE as an animal model.
To characterize the changes in global gene expression in the livers of H1/siRNAinsulin-CMV/hIDE transgenic (Tg) mice in response to the reduced bioavailability of insulin, total RNA extracted from the livers of 20-week-old Tg and non-Tg mice was converted to cDNA, labeled with biotin and hybridized to oligonucleotide microarrays. The microarray results were confirmed by a real-time reverse transcription-polymerase chain reaction. Two hundred and fifty-one and 73 genes were up- and down-regulated, respectively by insulin in H1/siRNAinsulin-CMV/hIDE Tg mice compared to the controls. Genes encoding for physiological processes, extracellular defense response and response to biotic stimuli were significantly over-represented in the up-regulated group. Among the down-regulated transcripts, those encoding for extracellular matrix proteins were dramatically over-represented, followed by those related to monooxygenase and oxidoreductase activities. The major genes in the up-regulated categories included Egr1, Saa2, Atf3, DNAJB1 and cCL2, whereas those in the down-regulated categories were Cyp17a1, Adn, Gadd45g, Eno3 and Moxd1. These results indicate that the microarray analysis identifies several gene functional groups and individual genes that respond to a sustained reduction in the insulin levels in the livers of Tg mice. These results also suggest that microarray testing is a useful tool for the better understanding of insulin-regulated diabetes-related diseases.
Jee
Seungwan
S
Laboratory Animal Resources Team, National Institute of Toxicological Research, Korea FDA, Seoul 122-704, Korea.
Hwang
Daeyoun
D
Seo
Sujin
S
Kim
Yongkyu
Y
Kim
Chuelkyu
C
Kim
Byungguk
B
Shim
Sunbo
S
Lee
Suhae
S
Sin
Jisoon
J
Bae
Changjun
C
Lee
Byoungchun
B
Jang
Meekyung
M
Kim
Minsun
M
Yim
Suyoun
S
Jang
Insurk
I
Cho
Jungsik
J
Chae
Kabryong
K
D000818:Animals; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D007339:Insulysin / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*
D007328:Insulin; D034741:RNA, Small Interfering; D007339:Insulysin