Scn5a^tm2.1Care

Exon 28 was replaced with a modified exon in which nucleotide substitution results in the amino acid substitution of a stop codon for serine at position 2017 (S2017X). This mutation truncates the last three amino acids that constitute a PDZ domain. Cre-mediated recombination removed the floxed neomycin selection cassette inserted upstream of the modified exon. Western blot analysis showed a ~25% reduction of protein levels in cardiac ventricular tissue from homozygous mutant mice relative to wild-type controls. mRNA quantification showed no significant changes in ventricular tissue, suggesting that reduced protein expression is due to changes in posttranslational regulation. Immunostaining of cardiac ventricular sections and isolated cardiomyocytes revealed that protein expression is specifically reduced at the cardiomyocyte lateral membrane but remains normal within the intercalated disk region. (J:224433)