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Growth and muscle defects in mice lacking adult myosin heavy chain genes.

Acakpo-Satchivi LJ, Edelmann W, Sartorius C, Lu BD, Wahr PA, Watkins SC, Metzger JM, Leinwand L, Kucherlapati R - J. Cell Biol. (1997)

Bottom Line: The three adult fast myosin heavy chains (MyHCs) constitute the vast majority of the myosin in adult skeletal musculature, and are >92% identical.Both strains exhibit growth and muscle defects, but the defects are different between the two strains and do not correlate with the abundance or distribution of each gene product.Most striking is that while both strains exhibit physiological defects in isolated muscles, the defects are distinct.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Albert Einstein College of Medicine, New York 10461, USA.

ABSTRACT
The three adult fast myosin heavy chains (MyHCs) constitute the vast majority of the myosin in adult skeletal musculature, and are >92% identical. We describe mice carrying mutations in each of two predominant adult fast MyHC genes, IIb and IId/x. Both strains exhibit growth and muscle defects, but the defects are different between the two strains and do not correlate with the abundance or distribution of each gene product. For example, despite the fact that MyHC-IIb accounts for >70% of the myosin in skeletal muscle and shows the broadest distribution of expression, the phenotypes of IIb mutants are generally milder than in the MyHC-IId/x strain. In addition, in a muscle which expresses both IIb and IId/x MyHC in wild-type mice, the histological defects are completely different for expression of the two genes. Most striking is that while both strains exhibit physiological defects in isolated muscles, the defects are distinct. Muscle from IIb mice has significantly reduced ability to generate force while IId mouse muscle generates normal amounts of force, but has altered kinetic properties. Many of the phenotypes demonstrated by these mice are typical in human muscle disease and should provide insight into their etiology.

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Related in: MedlinePlus

Hindlimb grip strength measurements in MyHC-IIb  and IId/x mice. Peak grip strengths were measured on the hindlimbs of mice. Five individual measurements were made for each  mouse. Each point in the graph represents the average of the five  measurements. There is a statistically significant difference (P <  0.01) between the combined average grip-strengths between −/−  and +/+ mice at 6 wk of age, but at 6 mo, only the IId/x  mice  exhibit sustained deficiencies in grip strength.
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Figure 5: Hindlimb grip strength measurements in MyHC-IIb and IId/x mice. Peak grip strengths were measured on the hindlimbs of mice. Five individual measurements were made for each mouse. Each point in the graph represents the average of the five measurements. There is a statistically significant difference (P < 0.01) between the combined average grip-strengths between −/− and +/+ mice at 6 wk of age, but at 6 mo, only the IId/x mice exhibit sustained deficiencies in grip strength.

Mentions: Based on an empirically assessed observation of muscle weakness in both MyHC mice at 4–6 wk of age, a study of the comparative fore- and hindlimb grip strengths of MyHC-IIb and IId/x mice was conducted. Five peak grip strength measurements for each mouse for fore- and hindlimbs were performed on +/+, +/−, and −/− mice at 6 wk of age, and at 6 mo of age. Fig. 5 shows the hindlimb measurements for wild-type and animals at both time points. Heterozygotes were indistinguishable from wild-type (not shown). MyHC-IIb mice showed decreased grip strength in both sets of limbs at 6 wk of age, but by 6 mo of age, they were indistinguishable from wild type. At 6 wk, this difference was 20% for forelimb strength and 30% for hindlimb strength. For the MyHC-IId/x line, mice of both age groups showed significant sustained muscle weakness. At 6 wk, this difference was 25% for forelimb strength and 40% for hindlimb strength. This difference was maintained with age.


Growth and muscle defects in mice lacking adult myosin heavy chain genes.

Acakpo-Satchivi LJ, Edelmann W, Sartorius C, Lu BD, Wahr PA, Watkins SC, Metzger JM, Leinwand L, Kucherlapati R - J. Cell Biol. (1997)

Hindlimb grip strength measurements in MyHC-IIb  and IId/x mice. Peak grip strengths were measured on the hindlimbs of mice. Five individual measurements were made for each  mouse. Each point in the graph represents the average of the five  measurements. There is a statistically significant difference (P <  0.01) between the combined average grip-strengths between −/−  and +/+ mice at 6 wk of age, but at 6 mo, only the IId/x  mice  exhibit sustained deficiencies in grip strength.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2140209&req=5

Figure 5: Hindlimb grip strength measurements in MyHC-IIb and IId/x mice. Peak grip strengths were measured on the hindlimbs of mice. Five individual measurements were made for each mouse. Each point in the graph represents the average of the five measurements. There is a statistically significant difference (P < 0.01) between the combined average grip-strengths between −/− and +/+ mice at 6 wk of age, but at 6 mo, only the IId/x mice exhibit sustained deficiencies in grip strength.
Mentions: Based on an empirically assessed observation of muscle weakness in both MyHC mice at 4–6 wk of age, a study of the comparative fore- and hindlimb grip strengths of MyHC-IIb and IId/x mice was conducted. Five peak grip strength measurements for each mouse for fore- and hindlimbs were performed on +/+, +/−, and −/− mice at 6 wk of age, and at 6 mo of age. Fig. 5 shows the hindlimb measurements for wild-type and animals at both time points. Heterozygotes were indistinguishable from wild-type (not shown). MyHC-IIb mice showed decreased grip strength in both sets of limbs at 6 wk of age, but by 6 mo of age, they were indistinguishable from wild type. At 6 wk, this difference was 20% for forelimb strength and 30% for hindlimb strength. For the MyHC-IId/x line, mice of both age groups showed significant sustained muscle weakness. At 6 wk, this difference was 25% for forelimb strength and 40% for hindlimb strength. This difference was maintained with age.

Bottom Line: The three adult fast myosin heavy chains (MyHCs) constitute the vast majority of the myosin in adult skeletal musculature, and are >92% identical.Both strains exhibit growth and muscle defects, but the defects are different between the two strains and do not correlate with the abundance or distribution of each gene product.Most striking is that while both strains exhibit physiological defects in isolated muscles, the defects are distinct.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Albert Einstein College of Medicine, New York 10461, USA.

ABSTRACT
The three adult fast myosin heavy chains (MyHCs) constitute the vast majority of the myosin in adult skeletal musculature, and are >92% identical. We describe mice carrying mutations in each of two predominant adult fast MyHC genes, IIb and IId/x. Both strains exhibit growth and muscle defects, but the defects are different between the two strains and do not correlate with the abundance or distribution of each gene product. For example, despite the fact that MyHC-IIb accounts for >70% of the myosin in skeletal muscle and shows the broadest distribution of expression, the phenotypes of IIb mutants are generally milder than in the MyHC-IId/x strain. In addition, in a muscle which expresses both IIb and IId/x MyHC in wild-type mice, the histological defects are completely different for expression of the two genes. Most striking is that while both strains exhibit physiological defects in isolated muscles, the defects are distinct. Muscle from IIb mice has significantly reduced ability to generate force while IId mouse muscle generates normal amounts of force, but has altered kinetic properties. Many of the phenotypes demonstrated by these mice are typical in human muscle disease and should provide insight into their etiology.

Show MeSH
Related in: MedlinePlus