| Primary Identifier | MGI:4836388 | Allele Type | Targeted |
| Attribute String | Hypomorph | Gene | Mybpc3 |
| Transmission | Germline | Strain of Origin | 129S2/SvPasCrl |
| Is Recombinase | false | Is Wild Type | false |
| molecularNote | A G-to-A mutation was introduced in exon 6 splice donor site (changing it from G-GT to A-GT) and a loxP site flanked neomycin resistance gene cassette was inserted into intron 6. Subsequent Cre-mediated recombination removed the neo cassette. RT-PCR detects three isoforms. Isoform mutant-1 splices normally and is predicted to produce a p.E264K 150 KDa protein. Isoform mutant-2 and mutant-3 lack exon 6, inducing a frameshift and premature stop codon. Isoform mutant-2 contains a premature termination codon in exon 9 (nonsense) and is predicted to produce a 32 KDa truncated protein, including 41 novel amino acids. Isoform mutant-3 retains 46 bp of intron 8 followed by a new cryptic acceptor splice site (deletion/insertion), which restores the reading frame and is predicted to produce a 147 KDa protein, containing an internal deletion and 41 novel amino acids. Isoform mutant-2 and -3 represent 50% of the total mRNA in homozygous mice. Western blot analysis detected all three predicted protein products. A greater than 80% reduction in total mRNA and protein levels was reported. |
