| First Author | Revelli JP | Year | 2011 |
| Journal | Obesity (Silver Spring) | Volume | 19 |
| Issue | 5 | Pages | 1010-8 |
| PubMed ID | 21127480 | Mgi Jnum | J:185493 |
| Mgi Id | MGI:5428944 | Doi | 10.1038/oby.2010.282 |
| Citation | Revelli JP, et al. (2011) Profound obesity secondary to hyperphagia in mice lacking kinase suppressor of ras 2. Obesity (Silver Spring) 19(5):1010-8 |
| abstractText | The kinase suppressor of ras 2 (KSR2) gene resides at human chromosome 12q24, a region linked to obesity and type 2 diabetes (T2D). While knocking out and phenotypically screening mouse orthologs of thousands of druggable human genes, we found KSR2 knockout (KSR2(-/-)) mice to be more obese and glucose intolerant than melanocortin 4 receptor(-/-) (MC4R(-/-)) mice. The obesity and T2D of KSR2(-/-) mice resulted from hyperphagia which was unresponsive to leptin and did not originate downstream of MC4R. The kinases AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) are each linked to food intake regulation, but only mTOR had increased activity in KSR2(-/-) mouse brain, and the ability of rapamycin to inhibit food intake in KSR2(-/-) mice further implicated mTOR in this process. The metabolic phenotype of KSR2 heterozygous (KSR2(+/minus;)) and KSR2(-/-) mice suggests that human KSR2 variants may contribute to a similar phenotype linked to human chromosome 12q24. |
