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Cyfip1 Haploinsufficiency Increases Compulsive-Like Behavior and Modulates Palatable Food Intake in Mice: Dependence on Cyfip2 Genetic Background, Parent-of Origin, and Sex.

ABSTRACT: 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.

SUBMITTER: Babbs RK

PROVIDER: S-EPMC6723122 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Cyfip1 Haploinsufficiency Increases Compulsive-Like Behavior and Modulates Palatable Food Intake in Mice: Dependence on Cyfip2 Genetic Background, Parent-of Origin, and Sex.

Babbs Richard K RK Beierle Jacob A JA Ruan Qiu T QT Kelliher Julia C JC Chen Melanie M MM Feng Ashley X AX Kirkpatrick Stacey L SL Benitez Fabiola A FA Rodriguez Fred A FA Pierre Johanne J JJ Anandakumar Jeya J Kumar Vivek V Mulligan Megan K MK Bryant Camron D CD

G3 (Bethesda, Md.) 20190904 9

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 d ...[more]

PMID: 31324746

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Project description:BackgroundChemical intolerance is a widespread public health problem characterized by symptoms that reportedly result from low-level exposure to chemicals. Although several studies have reported factors related to chemical intolerance in adults, the impact of family members has not been reported. In the present study, we investigated the background factors related to chemical intolerance in family members and parent-child relationships.MethodsWe distributed a self-reported questionnaire to 4325 mothers who were invited to visit the Kishiwada Health Center in Kishiwada City, Osaka, between January 2006 and December 2007 for the regular health checkup of their three-and-a-half-year-old children.ResultsThe prevalence of chemical intolerance in the 3-year-old children was almost one eighteenth of that reported by their mothers. Multiple logistic regression analyses revealed that cold sensitivity [odds ratio (OR), 1.89; 95% confidence interval (CI), 1.04-3.44], past bronchial asthma (OR, 2.84; 95% CI, 1.46-5.53), and any past allergies (OR, 2.21; 95% CI, 1.36-3.60) were significantly associated with chemical intolerance in the mother. The presence of indoor cat during childhood (OR, 1.99; 95% CI, 1.08-3.69) was significantly associated with chemical intolerance in the mother; however, the association was weak compared with cold sensitivity and past asthma and allergies. The current chemical intolerance of the mother was significantly associated with allergic rhinitis (OR, 2.32; 95% CI, 1.19-4.53), bronchial asthma (OR, 3.66; 95% CI, 2.00-6.69), and chronic bronchitis (OR, 3.69; 95% CI, 1.04-13.03) in her 3-year-old child.ConclusionsThe results suggest that inherent physical constitution and childhood housing environment are associated with a risk of acquiring chemical intolerance. Children of mothers with chemical intolerance have a possible risk of respiratory hypersensitivity or inflammation. Further investigation is recommended to determine the inherent physical constitution and background environmental factors associated with the risk of acquiring chemical intolerance. The impact of having mothers with chemical intolerance on the health of children also requires further study.

Dataset Information

Cyfip1 Haploinsufficiency Increases Compulsive-Like Behavior and Modulates Palatable Food Intake in Mice: Dependence on Cyfip2 Genetic Background, Parent-of Origin, and Sex.

Publications

<i>Cyfip1</i> Haploinsufficiency Increases Compulsive-Like Behavior and Modulates Palatable Food Intake in Mice: Dependence on <i>Cyfip2</i> Genetic Background, Parent-of Origin, and Sex.

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