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

Autor: Cleverley K; Department of Neuromuscular Diseases, Queen Square Institute of Neurology, London, UK., Lee WC; Department of Neuromuscular Diseases, Queen Square Institute of Neurology, London, UK., Mumford P; Department of Neuromuscular Diseases, Queen Square Institute of Neurology, London, UK.; The UK Dementia Research Institute, University College London, Queen Square, London, WC1N 3BG, UK., Collins T; Department of Neuromuscular Diseases, Queen Square Institute of Neurology, London, UK., Rickman M; Department of Neuromuscular Diseases, Queen Square Institute of Neurology, London, UK., Cunningham TJ; Mammalian Genetics Unit, Harwell, UK., Cleak J; Mammalian Genetics Unit, Harwell, UK., Mianne J; Mary Lyon Centre, MRC Harwell Institute, Oxfordshire, OX11 0RD, UK., Szoke-Kovacs Z; Mary Lyon Centre, MRC Harwell Institute, Oxfordshire, OX11 0RD, UK., Stewart M; Mammalian Genetics Unit, Harwell, UK., Teboul L; Mammalian Genetics Unit, Harwell, UK., Maduro C; Department of Neuromuscular Diseases, Queen Square Institute of Neurology, London, UK., Wells S; Mary Lyon Centre, MRC Harwell Institute, Oxfordshire, OX11 0RD, UK., Wiseman FK; Department of Neuromuscular Diseases, Queen Square Institute of Neurology, London, UK.; The UK Dementia Research Institute, University College London, Queen Square, London, WC1N 3BG, UK., Fisher EMC; Department of Neuromuscular Diseases, Queen Square Institute of Neurology, London, UK. elizabeth.fisher@ucl.ac.uk.
Jazyk: angličtina
Zdroj: Mammalian genome : official journal of the International Mammalian Genome Society [Mamm Genome] 2021 Apr; Vol. 32 (2), pp. 94-103. Date of Electronic Publication: 2021 Mar 13.
DOI: 10.1007/s00335-021-09864-6
Abstrakt: 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.
Databáze: MEDLINE
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