PMID- 10532952
OWN - NLM
STAT- MEDLINE
DCOM- 19991116
LR  - 20190706
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 85
IP  - 9
DP  - 1999 Oct 29
TI  - In vivo modeling of myosin binding protein C familial hypertrophic
      cardiomyopathy.
PG  - 841-7
AB  - Myosin binding protein C (MyBP-C) is an integral part of the striated muscle
      sarcomere. As is the case for other sarcomeric genes in human populations,
      multiple mutations within the gene have been linked to familial hypertrophic
      cardiomyopathy. Although some MyBP-C lesions are the result of missense
      mutations, most show truncated polypeptides lacking either the myosin or myosin
      and titin binding sites. Previously, we generated transgenic (TG) mice with
      cardiac-specific expression of a MyBP-C mutant lacking the myosin and titin
      binding domains. Surprisingly, the mutant protein was stable and made up a
      majority of the MyBP-C species, with concomitant reductions in endogenous MyBP-C 
      such that overall MyBP-C stoichiometry was conserved. In the present study, we
      created a second series of TG mice that express, in the heart, a mutant MyBP-C
      lacking only the myosin binding site. In contrast to the previous data for the
      MyBP-C lacking both titin and myosin binding sites, only very modest levels of
      protein were found, consistent with data obtained from human biopsies in which
      mutated MyBP-C could not be detected. Despite normal levels of wild-type MyBP-C, 
      there were significant changes in the structure and ultrastructure of the heart. 
      Fiber mechanics showed decreased unloading shortening velocity, maximum
      shortening velocity, and relative maximal power output.
FAU - Yang, Q
AU  - Yang Q
AD  - Department of Pediatrics, Division of Molecular Cardiovascular Biology,
      Children's Hospital Research Foundation, Cincinnati, Ohio 45229-3039, USA.
FAU - Sanbe, A
AU  - Sanbe A
FAU - Osinska, H
AU  - Osinska H
FAU - Hewett, T E
AU  - Hewett TE
FAU - Klevitsky, R
AU  - Klevitsky R
FAU - Robbins, J
AU  - Robbins J
LA  - eng
SI  - GENBANK/AF059576
GR  - HL41496/HL/NHLBI NIH HHS/United States
GR  - HL56370/HL/NHLBI NIH HHS/United States
GR  - HL56620/HL/NHLBI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Carrier Proteins)
RN  - 0 (myosin-binding protein C)
RN  - EC 3.6.4.1 (Myosins)
SB  - IM
MH  - Animals
MH  - Binding Sites/genetics
MH  - Cardiomyopathy, Hypertrophic/*genetics/metabolism/physiopathology
MH  - Carrier Proteins/*genetics/metabolism
MH  - Disease Models, Animal
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Mutation
MH  - Myocardial Contraction/genetics
MH  - Myosins/metabolism
MH  - Protein Binding
EDAT- 1999/10/26 00:00
MHDA- 1999/10/26 00:01
CRDT- 1999/10/26 00:00
PHST- 1999/10/26 00:00 [pubmed]
PHST- 1999/10/26 00:01 [medline]
PHST- 1999/10/26 00:00 [entrez]
AID - 10.1161/01.res.85.9.841 [doi]
PST - ppublish
SO  - Circ Res. 1999 Oct 29;85(9):841-7. doi: 10.1161/01.res.85.9.841.