PMID- 10587521
OWN - NLM
STAT- MEDLINE
DCOM- 20000104
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 104
IP  - 11
DP  - 1999 Dec
TI  - A nemaline myopathy mutation in alpha-tropomyosin causes defective regulation of 
      striated muscle force production.
PG  - 1575-81
AB  - Nemaline myopathy (NM) is a rare autosomal dominant skeletal muscle myopathy
      characterized by severe muscle weakness and the subsequent appearance of nemaline
      rods within the muscle fibers. Recently, a missense mutation inTPM3, which
      encodes the slow skeletal alpha-tropomyosin (alphaTm), was linked to NM in a
      large kindred with an autosomal-dominant, childhood-onset form of the disease. We
      used adenoviral gene transfer to fully differentiated rat adult myocytes in vitro
      to determine the effects of NM mutant human alphaTm expression on striated muscle
      sarcomeric structure and contractile function. The mutant alphaTm was expressed
      and incorporated correctly into sarcomeres of adult muscle cells. The primary
      defect caused by expression of the mutant alphaTm was a decrease in the
      sensitivity of contraction to activating Ca(2+), which could help explain the
      hypotonia seen in NM. Interestingly, NM mutant alphaTm expression did not
      directly result in nemaline rod formation, which suggests that rod formation is
      secondary to contractile dysfunction and that load-dependent processes are likely
      involved in nemaline rod formation in vivo.
FAU - Michele, D E
AU  - Michele DE
AD  - Department of Physiology, University of Michigan, Ann Arbor, Michigan 48109, USA.
FAU - Albayya, F P
AU  - Albayya FP
FAU - Metzger, J M
AU  - Metzger JM
LA  - eng
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  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Tropomyosin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Amino Acid Sequence
MH  - Animals
MH  - Calcium/metabolism
MH  - Cells, Cultured
MH  - Female
MH  - Fluorescent Antibody Technique
MH  - Gene Transfer Techniques
MH  - Heart/physiopathology
MH  - Humans
MH  - Microscopy, Electron
MH  - Microscopy, Fluorescence
MH  - Molecular Sequence Data
MH  - Muscle Contraction/genetics
MH  - Muscle Weakness/genetics
MH  - Muscle, Skeletal/*physiopathology
MH  - Mutation
MH  - Myopathies, Nemaline/*genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sequence Alignment
MH  - Tropomyosin/*genetics
PMC - PMC409864
EDAT- 1999/12/10 00:00
MHDA- 1999/12/10 00:01
CRDT- 1999/12/10 00:00
PHST- 1999/12/10 00:00 [pubmed]
PHST- 1999/12/10 00:01 [medline]
PHST- 1999/12/10 00:00 [entrez]
AID - 10.1172/JCI7842 [doi]
PST - ppublish
SO  - J Clin Invest. 1999 Dec;104(11):1575-81. doi: 10.1172/JCI7842.