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A deletion containing a CTCF-element in intron 8 of the Bbs7 gene is partially responsible for juvenile obesity in the Berlin Fat Mouse

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Item Type:Article
Title:A deletion containing a CTCF-element in intron 8 of the Bbs7 gene is partially responsible for juvenile obesity in the Berlin Fat Mouse
Creators Name:Krause, F. and Mohebian, K. and Delpero, M. and Hesse, D. and Kuehn, R. and Arends, D. and Brockmann, G.A.
Abstract:The Berlin Fat Mouse Inbred (BFMI) line is a model for juvenile obesity. Previous studies on crosses between BFMI and C57Bl/6N (B6N) have identified a recessive defect causing juvenile obesity on chromosome 3 (jObes1). Bbs7 was identified as the most likely candidate gene for the observed effect. Comparative sequence analysis showed a 1578 bp deletion in intron 8 of Bbs7 in BFMI mice. A CTCF-element is located inside this deletion. To investigate the functional effect of this deletion, it was introduced into B6N mice using CRISPR/Cas9. Two mice containing the target deletion were obtained (B6N Bbs7(emI8∆1) and Bbs7(emI8∆2)) and were subsequently mated to BFMI and B6N to generate two families suitable for complementation. Inherited alleles were determined and body composition was measured by quantitative magnetic resonance. Evidence for a partial complementation (13.1-15.1%) of the jObes1 allele by the CRISPR/Cas9 modified B6N Bbs(7emI8∆1) and Bbs7(emI8∆2) alleles was found. Mice carrying the complementation alleles had a 23-27% higher fat-to-lean ratio compared to animals which have a B6N allele (P(Bbs7emI8∆1) = 4.25 × 10(-7); P(Bbs7emI8∆2) = 3.17 × 10(-5)). Consistent with previous findings, the recessive effect of the BFMI allele was also seen for the B6N Bbs(7emI8∆1) and Bbs(7emI8∆2) alleles. However, the effect size of the B6N Bbs(7emI8∆1) and Bbs(7emI8∆2) alleles was smaller than the BFMI allele, and thus showed only a partial complementation. Findings suggest additional variants near Bbs7 in addition to or interacting with the deletion in intron 8.
Keywords:Signal Transducing Adaptor Proteins, Cytoskeletal Proteins, Introns, Inbred Strains Mice, Obesity, Animals, Mice
Source:Mammalian Genome
ISSN:0938-8990
Publisher:Springer
Volume:33
Number:3
Page Range:465–470
Date:September 2021
Official Publication:http://doi.org/10.1007/s00335-021-09938-5
PubMed:View item in PubMed

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