Henmt1^pin

The molecular lesion is a T-to-A substitution in the conserved GT splice donor site at the 5 end of intron 3. This results in the splicing out of exon 3 from transcripts and the in-frame deletion of 43 amino acids from the putative methyltransferase domain of the encoded protein in two of the three predicted splice variants. RNA-Seq data confirmed exon 3 deletion occurred in virtually all transcripts within homozygous mutant germ cells. Transcript 1 and 2 expression (ENSMUST00000059946 and ENSMUST00000098680) were reduced by 93% and 94% in mutant spermatoctyes and spermatids; transcript 3 (GRCm38/mm10), which does not contain exon 3, was up-regulated in mutant spermatocytes and round spermatids. Western blotting suggests that isoform 1 (49kDa) is predominant isoform present in the wild type mouse testis and the mutant testes contained no detectable encoded protein. (J:228973)