The collaborative cross mouse for studying the effect of host genetic background on memory impairments due to obesity and diabetes  

作　　者：Avia Paz Kareem Midlej Osayd Zohud Iqbal MLone Fuad A.Iraqi 

机构地区：[1]Department of Clinical Microbiology and Immunology,Sackler Faculty of Medicine,Tel Aviv University,Tel Aviv,Israel

出　　处：《Animal Models and Experimental Medicine》2025年第1期126-141,共16页动物模型与实验医学(英文)

基　　金：Tel-Aviv University(TAU)。

摘　　要：Background:Over the past few decades,a threefold increase in obesity and type 2 diabetes(T2D)has placed a heavy burden on the health-care system and society.Previous studies have shown correlations between obesity,T2D,and neurodegenera-tive diseases,including dementia.It is imperative to further understand the relation-ship between obesity,T2D,and cognitive deficits.Methods:This investigation tested and evaluated the cognitive impact of obesity and T2D induced by high-fat diet(HFD)and the effect of the host genetic background on the severity of cognitive decline caused by obesity and T2D in collaborative cross(CC)mice.The CC mice are a genetically diverse panel derived from eight inbred strains.Results:Our findings demonstrated significant variations in the recorded phenotypes across different CC lines compared to the reference mouse line,C57BL/6J.CC037 line exhibited a substantial increase in body weight on HFD,whereas line CC005 ex-hibited differing responses based on sex.Glucose tolerance tests revealed significant variations,with some lines like CC005 showing a marked increase in area under the curve(AUC)values on HFD.Organ weights,including brain,spleen,liver,and kidney,varied significantly among the lines and sexes in response to HFD.Behavioral tests using the Morris water maze indicated that cognitive performance was differentially affected by diet and genetic background.Conclusions:Our study establishes a foundation for future quantitative trait loci map-ping using CC lines and identifying genes underlying the comorbidity of Alzheimer's disease(AD),caused by obesity and T2D.The genetic components may offer new tools for early prediction and prevention.

关 键 词：collaborative cross mouse DIABETES host genetic background memory impairments OBESITY 

分 类 号：R587.1[医药卫生—内分泌] R589.2[医药卫生—内科学] R-332[医药卫生—临床医学]