RRC ID 53817
Author Chisada S, Kurokawa T, Murashita K, Rønnestad I, Taniguchi Y, Toyoda A, Sakaki Y, Takeda S, Yoshiura Y.
Title Leptin receptor-deficient (knockout) medaka, Oryzias latipes, show chronical up-regulated levels of orexigenic neuropeptides, elevated food intake and stage specific effects on growth and fat allocation.
Journal Gen Comp Endocrinol
Abstract The first studies that identified leptin and its receptor (LepR) in mammals were based on mutant animals that displayed dramatic changes in body-weight and regulation of energy homeostasis. Subsequent studies have shown that a deficiency of leptin or LepR in homoeothermic mammals results in hyperphagia, obesity, infertility and a number of other abnormalities. The physiological roles of leptin-mediated signaling in ectothermic teleosts are still being explored. Here, we produced medaka with homozygous LepR gene mutation using the targeting induced local lesions in a genome method. This knockout mutant had a point mutation of cysteine for stop codon at the 357th amino acid just before the leptin-binding domain. The evidence for loss of function of leptin-mediated signaling in the mutant is based on a lack of response to feeding in the expression of key appetite-related neuropeptides in the diencephalon. The mutant lepr−/− medaka expressed constant up-regulated levels of mRNA for the orexigenic neuropeptide Ya and agouti-related protein and a suppressed level of anorexigenic proopiomelanocortin 1 in the diencephalon independent of feeding, which suggests that the mutant did not possess functional LepR. Phenotypes of the LepR-mutant medaka were analyzed in order to understand the effects on food intake, growth, and fat accumulation in the tissues. The food intake of the mutant medaka was higher in post-juveniles and adult stages than that of wild-type (WT) fish. The hyperphagia led to a high growth rate at the post-juvenile stage, but did not to significant alterations in final adult body size. There was no additional deposition of fat in the liver and muscle in the post-juvenile and adult mutants, or in the blood plasma in the adult mutant. However, adult LepR mutants possessed large deposits of visceral fat, unlike in the WT fish, in which there were none. Our analysis confirms that LepR in medaka exert a powerful influence on the control on food intake. Further analyses using the mutant will contribute to a better understanding of the role of leptin in fish. This is the first study to produce fish with leptin receptor deficiency.
Volume 195
Pages 9-20
Published 2014-1-1
PMID 24505600
MeSH Agouti-Related Protein / metabolism Animals Animals, Genetically Modified / growth & development* Animals, Genetically Modified / metabolism Appetite / drug effects Appetite / physiology Body Weight / drug effects* Diencephalon / drug effects Diencephalon / metabolism Eating / drug effects Eating / physiology* Gene Knockout Techniques* Hyperphagia / genetics Hyperphagia / pathology Intra-Abdominal Fat / drug effects* Leptin / metabolism Mutation / genetics Neuropeptides / pharmacology* Obesity / metabolism Oryzias / genetics Oryzias / growth & development Oryzias / metabolism Receptors, Leptin / physiology* Up-Regulation
IF 2.428
Times Cited 39
Medaka LepR(C357X) (MT996)