The structural basis of alpha-tropomyosin linked (Asp230Asn) familial dilated cardiomyopathy.

ABSTRACT: Recently, linkage analysis of two large unrelated multigenerational families identified a novel dilated cardiomyopathy (DCM)-linked mutation in the gene coding for alpha-tropomyosin (TPM1) resulting in the substitution of an aspartic acid for an asparagine (at residue 230). To determine how a single amino acid mutation in α-tropomyosin (Tm) can lead to a highly penetrant DCM we generated a novel transgenic mouse model carrying the D230N mutation. The resultant mouse model strongly phenocopied the early onset of cardiomyopathic remodeling observed in patients as significant systolic dysfunction was observed by 2months of age. To determine the precise cellular mechanism(s) leading to the observed cardiac pathology we examined the effect of the mutation on Ca²⁺ handling in isolated

SUBMITTER: Lynn ML 

PROVIDER: S-EPMC5899615 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature