| First Author | Babbs RK | Year | 2019 |
| Journal | G3 (Bethesda) | Volume | 9 |
| Issue | 9 | Pages | 3009-3022 |
| PubMed ID | 31324746 | Mgi Jnum | J:280697 |
| Mgi Id | MGI:6369470 | Doi | 10.1534/g3.119.400470 |
| Citation | Babbs RK, et al. (2019) Cyfip1 Haploinsufficiency Increases Compulsive-Like Behavior and Modulates Palatable Food Intake in Mice: Dependence on Cyfip2 Genetic Background, Parent-of Origin, and Sex. G3 (Bethesda) 9(9):3009-3022 |
| abstractText | Binge eating (BE) is a heritable trait associated with eating disorders and involves episodes of rapid, large amounts of food consumption. We previously identified cytoplasmic FMR1-interacting protein 2 (Cyfip2) as a genetic factor underlying compulsive-like BE in mice. CYFIP2 is a homolog of CYFIP1 which is one of four paternally-deleted genes in patients with Type I Prader-Willi Syndrome (PWS), a neurodevelopmental disorder whereby 70% of cases involve paternal 15q11-q13 deletion. PWS symptoms include hyperphagia, obesity (if untreated), cognitive deficits, and obsessive-compulsive behaviors. We tested whether Cyfip1 haploinsufficiency (+/-) would enhance compulsive-like behavior and palatable food (PF) intake in a parental origin- and sex-dependent manner on two Cyfip2 genetic backgrounds, including the BE-prone C57BL/6N (Cyfip2 (N/N)) background and the BE-resistant C57BL/6J (Cyfip2 (J/J)) background. Cyfip1 (+/-) mice showed increased compulsive-like behavior on both backgrounds and increased PF intake on the Cyfip2 (N/N) background. In contrast, maternal Cyfip1 haploinsufficiency on the BE-resistant Cyfip2 (J/J) background induced a robust escalation in PF intake in wild-type Cyfip1 (J/J) males while having no effect in Cyfip1 (J/-) males. Notably, induction of behavioral phenotypes in wild-type males following maternal Fmr1 (+/-) has previously been reported. In the hypothalamus, there was a paternally-enhanced reduction in CYFIP1 protein whereas in the nucleus accumbens, there was a maternally-enhanced reduction in CYFIP1 protein. Nochange in FMR1 protein (FMRP) was observed in Cyfip1 (+/-) mice, regardless of parental origin. To summarize, Cyfip1 haploinsufficiency increased compulsive-like behavior and induced genetic background-dependent, sex-dependent, and parent-of-origin-dependent effects on PF consumption and CYFIP1 expression that could have relevance for neurodevelopmental and neuropsychiatric disorders. |
