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

Autor: Babbs RK; Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry., Beierle JA; Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry.; T32 NIGMS Training Program in Biomolecular Pharmacology.; Boston University's Transformative Training Program in Addiction Science (TTPAS), Biomedical Genetics, Boston University School of Medicine, Boston, MA 02118., Ruan QT; Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry.; T32 NIGMS Training Program in Biomolecular Pharmacology.; Boston University's Transformative Training Program in Addiction Science (TTPAS), Biomedical Genetics, Boston University School of Medicine, Boston, MA 02118., Kelliher JC; Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry., Chen MM; Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry., Feng AX; Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry., Kirkpatrick SL; Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry., Benitez FA; Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry., Rodriguez FA; Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry., Pierre JJ; Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry., Anandakumar J; Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry., Kumar V; The Jackson Laboratory, 600 Main St., Bar Harbor, ME 04609, and., Mulligan MK; Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, 71 S. Manassas St, Memphis, TN 38163., Bryant CD; Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry camron@bu.edu.
Jazyk: angličtina
Zdroj: G3 (Bethesda, Md.) [G3 (Bethesda)] 2019 Sep 04; Vol. 9 (9), pp. 3009-3022. Date of Electronic Publication: 2019 Sep 04.
DOI: 10.1534/g3.119.400470
Abstrakt: 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.
(Copyright © 2019 Babbs et al.)
Databáze: MEDLINE
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