Figure 1.

Schematic of (a) the genomic structure of wild-type MyBP-C, MyBP-C(LoxP), and MyBP-C(Neo) alleles, the RNAs produced by each allele, and (b) the structure of the MyBP-C proteins encoded by each allele. (a) Exons 29–32 of the murine cardiac MyBP-C gene are shown for each allele (see Methods). The mutations alter only exon 30; all other exons are identical. The black lines above each gene segment reflect the structure of the encoded RNA indicated in the 5′→3′ orientation; thick lines are exons incorporated into the RNA, thin lines indicate skipped segments of the gene not found in RNA. The genotypes of mice were determined with primers 1F, 1R, 2F, 2R, and 3R. Primers 4F and 4R were used to determine the structure of MyBP-C RNA; structures of the deduced RNAs are indicated above each allele. (b) The structure of carboxyl ends of the MyBP-C polypeptides encoded by MyBP-C(Neo) and MyBP-C(Lox) alleles were deduced from the sequences of RNA found in the left ventricles of homozygous mice bearing the indicated allele. The residues (between residues 1064 and 1111) of the wild-type protein are encoded by exon 30. Novel amino acid residues at the carboxyl end of the mutant proteins (bold) are encoded by altered reading of exon 30 (Lox) or exon 31 (Neo). The wild-type MyBP-C protein is 1270 amino acids whereas the MyBP-C(Lox) protein is 1240-amino acids long; the complete sequences of these 2 carboxyl ends are not shown. The carboxyl end of the analogous human mutation found in family NN (3) is shown for comparison. Differences between the family NN protein and the MyBP-C(Neo) protein reflect sequence differences between the mouse and human MyBP-C gene exon 31.