Loading...
Please wait, while we are loading the content...
Similar Documents
Online Data Supplement for Manuscript # 3689 HYPERTROPHIC CARDIOMYOPATHY IN CARDIAC MYOSIN BINDING PROTEIN-C ( cMyBP-C ) KNOCKOUT MICE
| Content Provider | Semantic Scholar |
|---|---|
| Author | Harris, Samantha P. Bartley, Christopher R. Hacker, Timothy A. McDonald, Kerry S. Douglas, Pamela S. Greaser, M. L. Powers, Patricia A. G. Moss, Richard L. |
| Copyright Year | 2002 |
| Abstract | Familial hypertrophic cardiomyopathy (FHC) is an inherited autosomal dominant disease caused by mutations in sarcomeric proteins. Among these, mutations that affect myosin binding protein-C (MyBP-C), an abundant component of the thick filaments, account for 20% to 30% of all mutations linked to FHC. However, the mechanisms by which MyBP-C mutations cause disease and the function of MyBP-C are not well understood. Therefore, to assess deficits due to elimination of MyBP-C, we used gene targeting to produce a knockout mouse that lacks MyBP-C in the heart. Knockout mice were produced by deletion of exons 3 to 10 from the endogenous cardiac (c) MyBP-C gene in murine embryonic stem (ES) cells and subsequent breeding of chimeric founder mice to obtain mice heterozygous ( / ) and homozygous ( / ) for the knockout allele. Wild-type ( / ), cMyBP-C / , and cMyBP-C / mice were born in accordance with Mendelian inheritance ratios, survived into adulthood, and were fertile. Western blot analyses confirmed that cMyBP-C was absent in hearts of homozygous knockout mice. Whereas cMyBP-C / mice were indistinguishable from wild-type littermates, cMyBP-C / mice exhibited significant cardiac hypertrophy. Cardiac function, assessed using 2-dimensionally guided M-mode echocardiography, showed significantly depressed indices of diastolic and systolic function only in cMyBP-C / mice. Ca sensitivity of tension, measured in single skinned myocytes, was reduced in cMyBP-C / but not cMyBP-C / mice. These results establish that cMyBP-C is not essential for cardiac development but that the absence of cMyBP-C results in profound cardiac hypertrophy and impaired contractile function. (Circ Res. 2002;90:594-601.) |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://circres.ahajournals.org/content/circresaha/90/5/594.full.pdf?download=true |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
