A novel knockout mouse for the small EDRK-rich factor 2 (Serf2) showing developmental and other deficits

一种新型小 EDRK 富集因子 2 (Serf2) 基因敲除小鼠,表现出发育和其他缺陷

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作者:Karen Cleverley, Weaverly Colleen Lee, Paige Mumford, Toby Collins, Matthew Rickman, Thomas J Cunningham, James Cleak, Joffrey Mianne, Zsombor Szoke-Kovacs, Michelle Stewart, Lydia Teboul, Cheryl Maduro, Sara Wells, Frances K Wiseman, Elizabeth M C Fisher

Abstract

The small EDRK-rich factor 2 (SERF2) is a highly conserved protein that modifies amyloid fibre assembly in vitro and promotes protein misfolding. However, the role of SERF2 in regulating age-related proteotoxicity remains largely unexplored due to a lack of in vivo models. Here, we report the generation of Serf2 knockout mice using an ES cell targeting approach, with Serf2 knockout alleles being bred onto different defined genetic backgrounds. We highlight phenotyping data from heterozygous Serf2+/- mice, including unexpected male-specific phenotypes in startle response and pre-pulse inhibition. We report embryonic lethality in Serf2-/- null animals when bred onto a C57BL/6 N background. However, homozygous null animals were viable on a mixed genetic background and, remarkably, developed without obvious abnormalities. The Serf2 knockout mice provide a powerful tool to further investigate the role of SERF2 protein in previously unexplored pathophysiological pathways in the context of a whole organism.

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