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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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Growth rates of MyHC-IIb and IId/x mice. Weight  measurements for wild-type (▪), heterozygous (▴), and homozygous (○) male animals were taken once a week for a time period  of 100 d. The homozygous  mice weigh significantly less than  their +/+ or +/− littermates. Asterisks indicate time points at  which a statistically significant difference (P < 0.05) exists between combined average +/+ and −/− body weights. For the IIb  mice, n = 14, 4, and 4; for the IId/x mice, n = 14, 7, and 8 for wild-type, heterozygous, and homozygous mice, respectively.
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Figure 4: Growth rates of MyHC-IIb and IId/x mice. Weight measurements for wild-type (▪), heterozygous (▴), and homozygous (○) male animals were taken once a week for a time period of 100 d. The homozygous mice weigh significantly less than their +/+ or +/− littermates. Asterisks indicate time points at which a statistically significant difference (P < 0.05) exists between combined average +/+ and −/− body weights. For the IIb mice, n = 14, 4, and 4; for the IId/x mice, n = 14, 7, and 8 for wild-type, heterozygous, and homozygous mice, respectively.

Mentions: Both MyHC-IIb−/− and MyHC-IId/x−/− animals were significantly smaller in size than their +/− and +/+ littermates by 10 wk of age. wild-type, heterozygous, and homozygous male mice were weighed once a week for a period of 100 d. The data, shown in Fig. 4, reveal that, by 40 d of postnatal life, the −/− mice begin to show consistent growth retardation. By 100 d of age, they have an average weight ∼20% less than their +/+ and +/+ littermates. To determine whether the lower body weight was due to decreased muscle mass, the masses of 8 muscle groups were determined for −/−, +/−, and +/+ animals from the MyHC-IId/x line at 6 wk of age. Tibial lengths were also determined. These data are shown in Table I. The tibial lengths for all three groups in the IId/x mice were nearly identical, indicating that the differences in body weight were not due to a bony skeletal developmental defect, or retardation in bone growth. Three of the eight muscle groups had significantly lower muscle mass than the +/− mice; however, no quantitative correlation could be made between the decreased muscle mass and the reported IId/x MyHC content of wild-type muscle. In the case of the IIb mice, there was also nonuniform decrease in muscle mass. However, different muscles relative to the IId/x−/− were affected and to a greater degree than in IId−/− mice. For example, gastrocnemius and vastus lateralis in IIb−/− mice were both <+/− the mass of +/+, while the tibialis anterior was of normal mass (not shown). This is despite the fact that all three muscles have high MyHC-IIb content in the wild type mouse.


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)

Growth rates of MyHC-IIb and IId/x mice. Weight  measurements for wild-type (▪), heterozygous (▴), and homozygous (○) male animals were taken once a week for a time period  of 100 d. The homozygous  mice weigh significantly less than  their +/+ or +/− littermates. Asterisks indicate time points at  which a statistically significant difference (P < 0.05) exists between combined average +/+ and −/− body weights. For the IIb  mice, n = 14, 4, and 4; for the IId/x mice, n = 14, 7, and 8 for wild-type, heterozygous, and homozygous mice, respectively.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: Growth rates of MyHC-IIb and IId/x mice. Weight measurements for wild-type (▪), heterozygous (▴), and homozygous (○) male animals were taken once a week for a time period of 100 d. The homozygous mice weigh significantly less than their +/+ or +/− littermates. Asterisks indicate time points at which a statistically significant difference (P < 0.05) exists between combined average +/+ and −/− body weights. For the IIb mice, n = 14, 4, and 4; for the IId/x mice, n = 14, 7, and 8 for wild-type, heterozygous, and homozygous mice, respectively.
Mentions: Both MyHC-IIb−/− and MyHC-IId/x−/− animals were significantly smaller in size than their +/− and +/+ littermates by 10 wk of age. wild-type, heterozygous, and homozygous male mice were weighed once a week for a period of 100 d. The data, shown in Fig. 4, reveal that, by 40 d of postnatal life, the −/− mice begin to show consistent growth retardation. By 100 d of age, they have an average weight ∼20% less than their +/+ and +/+ littermates. To determine whether the lower body weight was due to decreased muscle mass, the masses of 8 muscle groups were determined for −/−, +/−, and +/+ animals from the MyHC-IId/x line at 6 wk of age. Tibial lengths were also determined. These data are shown in Table I. The tibial lengths for all three groups in the IId/x mice were nearly identical, indicating that the differences in body weight were not due to a bony skeletal developmental defect, or retardation in bone growth. Three of the eight muscle groups had significantly lower muscle mass than the +/− mice; however, no quantitative correlation could be made between the decreased muscle mass and the reported IId/x MyHC content of wild-type muscle. In the case of the IIb mice, there was also nonuniform decrease in muscle mass. However, different muscles relative to the IId/x−/− were affected and to a greater degree than in IId−/− mice. For example, gastrocnemius and vastus lateralis in IIb−/− mice were both <+/− the mass of +/+, while the tibialis anterior was of normal mass (not shown). This is despite the fact that all three muscles have high MyHC-IIb content in the wild type mouse.

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