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: PMID:23800849   (View Abstract at PubMed)
DOI: DOI:10.1152/physiolgenomics.00040.2013   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Insulin Resistance  IMP 8549777; 8549777 RGD 
Insulin Resistance  ISOLep (Rattus norvegicus)8549777; 8549777DNA:nonsense mutation:cds:RGD 
Insulin Resistance  IMP 8549777DNA:nonsense mutation:cds:RGD 
obesity  IMP 8549777; 8549777 RGD 
obesity  ISOLep (Rattus norvegicus)8549777; 8549777DNA:nonsense mutation:cds:RGD 
obesity  IMP 8549777DNA:nonsense mutation:cds:RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
increased circulating cholesterol level  IMP 8549777; 8549777 RGD 
increased circulating cholesterol level  IMP 8549777DNA:nonsense mutation:cds:RGD 
increased circulating triglyceride level  IMP 8549777; 8549777 RGD 
increased circulating triglyceride level  IMP 8549777DNA:nonsense mutation:cds:RGD 
increased liver triglyceride level  IMP 8549777; 8549777 RGD 
increased liver triglyceride level  IMP 8549777DNA:nonsense mutation:cds:RGD 
Objects Annotated

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

Genes (Mus musculus)
Lep  (leptin)

Genes (Homo sapiens)
LEP  (leptin)

F344-Lepm1Kyo  (F344 OB rat)

Additional Information