机构：[1]Mammalian Genetics Unit and Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxon, UK[2]Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands[3]MRC London Institute of Medical Sciences, London, UK[4]MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK
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 Mg2+ 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.
基金：
We thank Dr Minghui Yin for assisting with the wound healing assay. Also I would like to thank Dr Liz Miller and her lab members for their help and support during revision. Funding was received from the Medical Research Council (MC_U142661184). Jeroen de B [MC_U142661184]; Medical Research Council [2017.81.014]; Dutch Diabetes Research Foundation [Vidi 09150172110040]; Netherlands Organization for Scientific Research [A410]; MRC [5UM1HG006348-08]; National Institutes for Health
第一作者机构：[1]Mammalian Genetics Unit and Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxon, UK[*1]MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Ave, Trumpington, Cambridge CB2 0QH, UK.
共同第一作者：
通讯作者：
通讯机构：[1]Mammalian Genetics Unit and Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxon, UK[*1]MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Ave, Trumpington, Cambridge CB2 0QH, UK.[*2]Mammalian Genetics Unit and Mary Lyon Centre, MRC Harwell Institute, Didcot, Oxon OX11 0RD, UK.
推荐引用方式(GB/T 7714)：
Bai Ying,Bentley Liz,Ma Chao,et al.Cleft palate and minor metabolic disturbances in a mouse global Arl15 gene knockout[J].FASEB JOURNAL.2023,37(11):doi:10.1096/fj.202201918R.
APA：
Bai, Ying,Bentley, Liz,Ma, Chao,Naveenan, Navaratnam,Cleak, James...&Cox, Roger D..(2023).Cleft palate and minor metabolic disturbances in a mouse global Arl15 gene knockout.FASEB JOURNAL,37,(11)
MLA：
Bai, Ying,et al."Cleft palate and minor metabolic disturbances in a mouse global Arl15 gene knockout".FASEB JOURNAL 37..11(2023)
生物学