Cleft palate and minor metabolic disturbances in a mouse global Arl15 gene knockout.

Autor: Bai Y; Mammalian Genetics Unit and Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxon, UK., Bentley L; Mammalian Genetics Unit and Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxon, UK., Ma C; Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands., Naveenan N; MRC London Institute of Medical Sciences, London, UK., Cleak J; Mammalian Genetics Unit and Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxon, UK., Wu Y; Mammalian Genetics Unit and Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxon, UK., Simon MM; Mammalian Genetics Unit and Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxon, UK., Westerberg H; Mammalian Genetics Unit and Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxon, UK., Cañas RC; Mammalian Genetics Unit and Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxon, UK., Horner N; Mammalian Genetics Unit and Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxon, UK., Pandey R; Mammalian Genetics Unit and Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxon, UK., Paphiti K; Mammalian Genetics Unit and Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxon, UK., Schulze U; MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK., Mianné J; Mammalian Genetics Unit and Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxon, UK., Hough T; Mammalian Genetics Unit and Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxon, UK., Teboul L; Mammalian Genetics Unit and Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxon, UK., de Baaij JHF; Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands., Cox RD; Mammalian Genetics Unit and Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxon, UK.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2023 Nov; Vol. 37 (11), pp. e23211.
DOI: 10.1096/fj.202201918R
Abstrakt: ARL15, a small GTPase protein, was linked to metabolic traits in association studies. We aimed to test the Arl15 gene as a functional candidate for metabolic traits in the mouse. CRISPR/Cas9 germline knockout (KO) of Arl15 showed that homozygotes were postnatal lethal and exhibited a complete cleft palate (CP). Also, decreased cell migration was observed from Arl15 KO mouse embryonic fibroblasts (MEFs). Metabolic phenotyping of heterozygotes showed that females had reduced fat mass on a chow diet from 14 weeks of age. Mild body composition phenotypes were also observed in heterozygous mice on a high-fat diet (HFD)/low-fat diet (LFD). Females on a HFD showed reduced body weight, gonadal fat depot weight and brown adipose tissue (BAT) weight. In contrast, in the LFD group, females showed increased bone mineral density (BMD), while males showed a trend toward reduced BMD. Clinical biochemistry analysis of plasma on HFD showed transient lower adiponectin at 20 weeks of age in females. Urinary and plasma Mg 2+ concentrations were not significantly different. Our phenotyping data showed that Arl15 is essential for craniofacial development. Adult metabolic phenotyping revealed potential roles in brown adipose tissue and bone development.
(© 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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