The collaborative cross mouse for studying the effect of host genetic background on memory impairments due to obesity and diabetes
Abstract 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 neurodegenerative diseases, including dementia. It is imperativ...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Animal Models and Experimental Medicine |
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| Online Access: | https://doi.org/10.1002/ame2.12488 |
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| author | Avia Paz Kareem Midlej Osayd Zohud Iqbal M. Lone Fuad A. Iraqi |
| author_facet | Avia Paz Kareem Midlej Osayd Zohud Iqbal M. Lone Fuad A. Iraqi |
| author_sort | Avia Paz |
| collection | DOAJ |
| description | Abstract 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 neurodegenerative diseases, including dementia. It is imperative to further understand the relationship 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 exhibited 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 mapping 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. |
| format | Article |
| id | doaj-art-1cf7c72f448a41bd8ca92bd5480c00a3 |
| institution | Kabale University |
| issn | 2576-2095 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Animal Models and Experimental Medicine |
| spelling | doaj-art-1cf7c72f448a41bd8ca92bd5480c00a32025-02-06T03:52:55ZengWileyAnimal Models and Experimental Medicine2576-20952025-01-018112614110.1002/ame2.12488The collaborative cross mouse for studying the effect of host genetic background on memory impairments due to obesity and diabetesAvia Paz0Kareem Midlej1Osayd Zohud2Iqbal M. Lone3Fuad A. Iraqi4Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine Tel Aviv University Tel Aviv IsraelDepartment of Clinical Microbiology and Immunology, Sackler Faculty of Medicine Tel Aviv University Tel Aviv IsraelDepartment of Clinical Microbiology and Immunology, Sackler Faculty of Medicine Tel Aviv University Tel Aviv IsraelDepartment of Clinical Microbiology and Immunology, Sackler Faculty of Medicine Tel Aviv University Tel Aviv IsraelDepartment of Clinical Microbiology and Immunology, Sackler Faculty of Medicine Tel Aviv University Tel Aviv IsraelAbstract 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 neurodegenerative diseases, including dementia. It is imperative to further understand the relationship 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 exhibited 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 mapping 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.https://doi.org/10.1002/ame2.12488collaborative cross mousediabeteshost genetic backgroundmemory impairmentsobesity |
| spellingShingle | Avia Paz Kareem Midlej Osayd Zohud Iqbal M. Lone Fuad A. Iraqi The collaborative cross mouse for studying the effect of host genetic background on memory impairments due to obesity and diabetes Animal Models and Experimental Medicine collaborative cross mouse diabetes host genetic background memory impairments obesity |
| title | The collaborative cross mouse for studying the effect of host genetic background on memory impairments due to obesity and diabetes |
| title_full | The collaborative cross mouse for studying the effect of host genetic background on memory impairments due to obesity and diabetes |
| title_fullStr | The collaborative cross mouse for studying the effect of host genetic background on memory impairments due to obesity and diabetes |
| title_full_unstemmed | The collaborative cross mouse for studying the effect of host genetic background on memory impairments due to obesity and diabetes |
| title_short | The collaborative cross mouse for studying the effect of host genetic background on memory impairments due to obesity and diabetes |
| title_sort | collaborative cross mouse for studying the effect of host genetic background on memory impairments due to obesity and diabetes |
| topic | collaborative cross mouse diabetes host genetic background memory impairments obesity |
| url | https://doi.org/10.1002/ame2.12488 |
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