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Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice.

ABSTRACT: Evidence has emerged that suggests a link between motor deficits, obesity and many neurological disorders. However, the contributing genetic risk factors are poorly understood. Here we used the Collaborative Cross (CC), a large panel of newly inbred mice that captures 90% of the known variation among laboratory mice, to identify the genetic loci controlling rotarod performance and its relationship with body weight in a cohort of 365 mice across 16 CC strains. Body weight and rotarod performance varied widely across CC strains and were significantly negatively correlated. Genetic linkage analysis identified 14 loci that were associated with body weight. However, 45 loci affected rotarod performance, seven of which were also associated with body weight, suggesting a strong link at the genetic level. Lastly, we show that genes identified in this study overlap significantly with those related to neurological disorders and obesity found in human GWA studies. In conclusion, our results provide a genetic framework for studies of the connection between body weight, the central nervous system and behavior.

SUBMITTER: Mao JH

PROVIDER: S-EPMC4637864 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice.

Mao Jian-Hua JH Langley Sasha A SA Huang Yurong Y Hang Michael M Bouchard Kristofer E KE Celniker Susan E SE Brown James B JB Jansson Janet K JK Karpen Gary H GH Snijders Antoine M AM

Scientific reports 20151109

Evidence has emerged that suggests a link between motor deficits, obesity and many neurological disorders. However, the contributing genetic risk factors are poorly understood. Here we used the Collaborative Cross (CC), a large panel of newly inbred mice that captures 90% of the known variation among laboratory mice, to identify the genetic loci controlling rotarod performance and its relationship with body weight in a cohort of 365 mice across 16 CC strains. Body weight and rotarod performance ...[more]

PMID: 26548763

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Project description:BackgroundBody weight concerns are common among individuals with eating disorders, and this construct can be assessed using psychometric instruments. The Weight Concerns Scale (WCS) is commonly used to assess body weight concerns.AimsTo evaluate the psychometric properties of the WCS with Brazilian, Portuguese, and Mozambican female college students; to estimate body weight concerns; and to identify factors related to eating disorders.MethodsConfirmatory factor analysis was performed. Factorial, convergent, concurrent, and divergent validity, as well as reliability, were assessed. Cross-national invariance was tested by means of multigroup analysis. Structural models were tested using the WCS as the dependent variable, while demographic and academic variables and body mass index were used as independent variables. Logistic models were tested to estimate the likelihood of eating disorders being developed in specific groups.ResultsParticipants were 2,068 female students. The psychometric properties of the WCS were adequate for the Portuguese sample; however, for the Brazilian and Mozambican samples, it was necessary to correlate the errors of two items to improve model fit. The WCS did not show cross-national invariance. The variables "thoughts about dropping out of college," "medication use because of studies," "medication and supplements use for body change," "body mass index," "socioeconomic status," "age," and "performance in course" were significant predictors of body weight concerns. Overall, 24.4% (95% confidence interval = 22.9-26.7) of the students were likely to develop eating disorders. Students under 21 years old, who use medication and supplements for body change, and who were classified as overweight/obese have increased likelihood of developing eating disorders.ConclusionThe WCS showed good psychometric properties with Brazilian, Portuguese, and Mozambican students; however, it did not show cross-national invariance. We identified important aspects for investigating body weight concerns and factors related to eating disorders.

Project description:Rift Valley fever (RVF) is an arboviral disease of humans and livestock responsible for severe economic and human health impacts. In humans, RVF spans a variety of clinical manifestations, ranging from an acute flu-like illness to severe forms of disease, including late-onset encephalitis. The large variations in human RVF disease are inadequately represented by current murine models, which overwhelmingly die of early-onset hepatitis. Existing mouse models of RVF encephalitis are either immunosuppressed, display an inconsistent phenotype, or develop encephalitis only when challenged via intranasal or aerosol exposure. In this study, the genetically defined recombinant inbred mouse resource known as the Collaborative Cross (CC) was used to identify mice with additional RVF disease phenotypes when challenged via a peripheral foot-pad route to mimic mosquito-bite exposure. Wild-type Rift Valley fever virus (RVFV) challenge of 20 CC strains revealed three distinct disease phenotypes: early-onset hepatitis, mixed phenotype, and late-onset encephalitis. Strain CC057/Unc, with the most divergent phenotype, which died of late-onset encephalitis at a median of 11 days post-infection, is the first mouse strain to develop consistent encephalitis following peripheral challenge. CC057/Unc mice were directly compared to C57BL/6 mice, which uniformly succumb to hepatitis within 2-4 days of infection. Encephalitic disease in CC057/Unc mice was characterized by high viral RNA loads in brain tissue, accompanied by clearance of viral RNA from the periphery, low ALT levels, lymphopenia, and neutrophilia. In contrast, C57BL/6 mice succumbed from hepatitis at 3 days post-infection with high viral RNA loads in the liver, viremia, high ALT levels, lymphopenia, and thrombocytopenia. The identification of a strain of CC mice as an RVFV encephalitis model will allow for future investigation into the pathogenesis and treatment of RVF encephalitic disease and indicates that genetic background makes a major contribution to RVF disease variation.

Dataset Information

Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice.

Publications

Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice.

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