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A novel knockout mouse for the small EDRK-rich factor 2 (Serf2) showing developmental and other deficits
Karen Cleverley1, Weaverly Colleen Lee1, Paige Mumford1,2
1Department of Neuromuscular Diseases, Queen Square Institute of Neurology, London, UK.
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.
Insights
Small EDRK-rich factor 2 (SERF2) knockout mice were generated to study its role in proteotoxicity. Homozygous null mice showed embryonic lethality on one background but were viable on another, offering new research avenues.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Small EDRK-rich factor 2 (SERF2) is a conserved protein influencing amyloid fiber assembly and protein misfolding.
- Its in vivo role in age-related proteotoxicity is understudied due to a lack of appropriate models.
Purpose of the Study:
- To generate and characterize Serf2 knockout mouse models to investigate SERF2's physiological functions.
- To explore the impact of SERF2 deficiency on proteotoxicity and age-related diseases in vivo.
Main Methods:
- Generation of Serf2 knockout mice using ES cell targeting.
- Breeding knockout alleles onto different genetic backgrounds (C57BL/6N and mixed).
- Phenotyping of heterozygous (Serf2+/-) and homozygous (Serf2-/-) mice.
Main Results:
- Heterozygous Serf2+/- mice exhibited male-specific alterations in startle response and pre-pulse inhibition.
- Homozygous Serf2-/- mice displayed embryonic lethality on a C57BL/6N background.
- Homozygous Serf2-/- mice were viable and developed without apparent abnormalities on a mixed genetic background.
Conclusions:
- Serf2 knockout mice are valuable tools for studying SERF2's role in organismal physiology and disease.
- Genetic background significantly influences the viability and phenotype of Serf2-deficient mice.
- Further research is warranted to elucidate SERF2's function in various pathophysiological pathways.
