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Bai, Ying; Bentley, Liz; Ma, Chao; Naveenan, Navaratnam; Cleak, James; Wu, Yixing; Simon, Michelle M.; Westerberg, Henrik; Cañas, Ramón Casero; Horner, Neil; Pandey, Rajesh; Paphiti, Keanu; Schulze, Ulrike; Mianné, Joffrey; Hough, Tertius; Teboul, Lydia; de Baaij, Jeroen H. F.; Cox, Roger D.

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

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  • Media type: E-Article
  • Title: Cleft palate and minor metabolic disturbances in a mouse global Arl15 gene knockout
  • Contributor: Bai, Ying; Bentley, Liz; Ma, Chao; Naveenan, Navaratnam; Cleak, James; Wu, Yixing; Simon, Michelle M.; Westerberg, Henrik; Cañas, Ramón Casero; Horner, Neil; Pandey, Rajesh; Paphiti, Keanu; Schulze, Ulrike; Mianné, Joffrey; Hough, Tertius; Teboul, Lydia; de Baaij, Jeroen H. F.; Cox, Roger D.
  • imprint: Wiley, 2023
  • Published in: The FASEB Journal
  • Language: English
  • DOI: 10.1096/fj.202201918r
  • ISSN: 0892-6638; 1530-6860
  • Keywords: Genetics ; Molecular Biology ; Biochemistry ; Biotechnology
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p><jats:italic>ARL15</jats:italic>, a small GTPase protein, was linked to metabolic traits in association studies. We aimed to test the <jats:italic>Arl15</jats:italic> gene as a functional candidate for metabolic traits in the mouse. CRISPR/Cas9 germline knockout (KO) of <jats:italic>Arl15</jats:italic> showed that homozygotes were postnatal lethal and exhibited a complete cleft palate (CP). Also, decreased cell migration was observed from <jats:italic>Arl15</jats:italic> 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<jats:sup>2+</jats:sup> concentrations were not significantly different. Our phenotyping data showed that <jats:italic>Arl15</jats:italic> is essential for craniofacial development. Adult metabolic phenotyping revealed potential roles in brown adipose tissue and bone development.</jats:p>