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

Autor: Krause F; Albrecht Daniel Thaer-Institute for Agricultural and Horticultural Sciences, Humboldt-Universität zu Berlin, Unter den Linden 6, 10099, Berlin, Germany., Mohebian K; Albrecht Daniel Thaer-Institute for Agricultural and Horticultural Sciences, Humboldt-Universität zu Berlin, Unter den Linden 6, 10099, Berlin, Germany., Delpero M; Albrecht Daniel Thaer-Institute for Agricultural and Horticultural Sciences, Humboldt-Universität zu Berlin, Unter den Linden 6, 10099, Berlin, Germany., Hesse D; Albrecht Daniel Thaer-Institute for Agricultural and Horticultural Sciences, Humboldt-Universität zu Berlin, Unter den Linden 6, 10099, Berlin, Germany., Kühn R; Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Str. 10, 13125, Berlin, Germany., Arends D; Albrecht Daniel Thaer-Institute for Agricultural and Horticultural Sciences, Humboldt-Universität zu Berlin, Unter den Linden 6, 10099, Berlin, Germany., Brockmann GA; Albrecht Daniel Thaer-Institute for Agricultural and Horticultural Sciences, Humboldt-Universität zu Berlin, Unter den Linden 6, 10099, Berlin, Germany. gudrun.brockmann@agrar.hu-berlin.de.
Jazyk: angličtina
Zdroj: Mammalian genome : official journal of the International Mammalian Genome Society [Mamm Genome] 2022 Sep; Vol. 33 (3), pp. 465-470. Date of Electronic Publication: 2021 Dec 15.
DOI: 10.1007/s00335-021-09938-5
Abstrakt: 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 Bbs7 emI8∆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 Bbs7 emI8∆1 and Bbs7 emI8∆2 alleles. However, the effect size of the B6N Bbs7 emI8∆1 and Bbs7 emI8∆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.
(© 2021. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje