| RRC ID |
28838
|
| Author |
Aizawa-Abe M, Ebihara K, Ebihara C, Mashimo T, Takizawa A, Tomita T, Kusakabe T, Yamamoto Y, Aotani D, Yamamoto-Kataoka S, Sakai T, Hosoda K, Serikawa T, Nakao K.
|
| Title |
Generation of leptin-deficient Lepmkyo/Lepmkyo rats and identification of leptin-responsive genes in the liver.
|
| Journal |
Physiol Genomics
|
| Abstract |
Leptin is one of the key molecules in maintaining energy homeostasis. Although genetically leptin-deficient Lep(ob)/Lep(ob) mice have greatly contributed to elucidating leptin physiology, the use of more than one species can improve the accuracy of analysis results. Using the N-ethyl-N-nitrosourea mutagenesis method, we generated a leptin-deficient Lep(mkyo)/Lep(mkyo) rat that had a nonsense mutation (Q92X) in leptin gene. Lep(mkyo)/Lep(mkyo) rats showed obese phenotypes including severe fatty liver, which were comparable to Lep(ob)/Lep(ob) mice. To identify genes that respond to leptin in the liver, we performed microarray analysis with Lep(mkyo)/Lep(mkyo) rats and Lep(ob)/Lep(ob) mice. We sorted out genes whose expression levels in the liver of Lep(mkyo)/Lep(mkyo) rats were changed from wild-type (WT) rats and were reversed toward WT rats by leptin administration. In this analysis, livers were sampled for 6 h, a relatively short time after leptin administration to avoid the secondary effect of metabolic changes such as improvement of fatty liver. We did the same procedure in Lep(ob)/Lep(ob) mice and selected genes whose expression patterns were common in rat and mouse. We verified their gene expressions by real-time quantitative PCR. Finally, we identified eight genes that primarily respond to leptin in the liver commonly in rat and mouse. These genes might be important for the effect of leptin in the liver.
|
| Volume |
45(17)
|
| Pages |
786-93
|
| Published |
2013-9-3
|
| DOI |
10.1152/physiolgenomics.00040.2013
|
| PII |
physiolgenomics.00040.2013
|
| PMID |
23800849
|
| MeSH |
Animals
Codon, Nonsense
Disease Models, Animal
Ethylnitrosourea / toxicity
Fatty Liver / genetics
Fatty Liver / pathology
Gene Expression*
Leptin / blood
Leptin / deficiency
Leptin / genetics*
Leptin / pharmacology
Lipid Metabolism / genetics
Liver / drug effects
Liver / physiology*
Male
Mice, Mutant Strains
Mutagenesis
Obesity / genetics*
Rats, Mutant Strains / genetics*
Real-Time Polymerase Chain Reaction
|
| IF |
2.749
|
| Times Cited |
8
|
|
WOS Category
|
PHYSIOLOGY
GENETICS & HEREDITY
CELL BIOLOGY
|
| Resource |
| Rats |
F344-Lepm1Kyo(strainID=995) |
