Mybpc3^tm2.1Lcrr
Targeted Allele Detail

Summary

• Symbol: Mybpc3^tm2.1Lcrr
• Name: myosin binding protein C, cardiac; targeted mutation 2.1, Lucie Carrier
• MGI ID: MGI:4836388
• Synonyms: MYBPC3^772G>A
• Gene: Mybpc3 Location: Chr2:90948489-90966861 bp, + strand Genetic Position: Chr2, 50.44 cM, cytoband E1
• Alliance: Mybpc3^tm2.1Lcrr page

Mutation origin

• Germline Transmission: Earliest citation of germline transmission: J:164934
• Parent Cell Line: AT1 (ES Cell)
• Strain of Origin: 129S2/SvPasCrl

Mutation description

• Allele Type: Targeted (Hypomorph)
• Mutations: Insertion, Single point mutation
• Mutation details: 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. (J:164934)

Disease models

Expression

In Structures Affected by this Mutation:

3 anatomical structure(s)

Find Mice (IMSR)

• Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)
• Carrying this Mutation: Mouse Strains: 0 strains available Cell Lines: 0 lines available
• Carrying any Mybpc3 Mutation: 43 strains or lines available

References

• Original: J:164934 Vignier N, et al., Nonsense-mediated mRNA decay and ubiquitin-proteasome system regulate cardiac myosin-binding protein C mutant levels in cardiomyopathic mice. Circ Res. 2009 Jul 31;105(3):239-48
• All: 26 reference(s)