RGD Reference Report - Generation of leptin-deficient Lepmkyo/Lepmkyo rats and identification of leptin-responsive genes in the liver. - Rat Genome Database

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Generation of leptin-deficient Lepmkyo/Lepmkyo rats and identification of leptin-responsive genes in the liver.

Authors: 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 
Citation: Aizawa-Abe M, etal., Physiol Genomics. 2013 Sep 3;45(17):786-93. doi: 10.1152/physiolgenomics.00040.2013. Epub 2013 Jun 25.
RGD ID: 8549777
Pubmed: (View Article at PubMed) PMID:23800849
DOI: Full-text: DOI:10.1152/physiolgenomics.00040.2013

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.



Disease Annotations    
Insulin Resistance  (IMP,ISO)
obesity  (IMP,ISO)

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Lep  (leptin)
Lepm1Kyo  (leptin; ENU induced mutant1, Kyo)

Genes (Mus musculus)
Lep  (leptin)

Genes (Homo sapiens)
LEP  (leptin)

Strains
F344-Lepm1Kyo  (F344 OB rat)


Additional Information