Generation of a transgenic mouse embryonic stem cell line expressing Dnmt1Y495C mutation associated with HSAN1E disorder

Abstract

DNMT1 Y495C is the most common mutation associated with hereditary sensory and autonomic neuropathy type 1E, and dementia. Here we employed non-homologous recombination and generated a mouse embryonic stem cell line carrying a transgene expressing DNMT1 Y495C mutation in the wild-type background. The resultant cell line, Dnmt1Y495C-1 showed increased transcript levels of the Oct4 and Sox2 pluripotency markers and Gata6 and Pax6 germ layer markers. This cell line showed normal karyotype, expression of the mutant Dnmt1 and wild-type transcripts in approximately equal ratios and is a useful model for studying the abnormal neurogenesis due to the DNMT1 Y495C mutation.