| RRC ID |
53817
|
| 著者 |
Chisada S, Kurokawa T, Murashita K, Rønnestad I, Taniguchi Y, Toyoda A, Sakaki Y, Takeda S, Yoshiura Y.
|
| タイトル |
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.
|
| ジャーナル |
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.
|
| 巻・号 |
195
|
| ページ |
9-20
|
| 公開日 |
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
|
| 引用数 |
39
|
| リソース情報 |
| メダカ |
LepR(C357X) (MT996) |
