| Table 1. Vertebrate phenotypes
and human myopathies associated with mutations and/or perturbed
levels of sarcomeric and sarcomeric-associated proteins |
|
|
Phenotypes in vertebrate |
|
|
model systems |
Human myopathies |
|
| Thin filament/ |
|
|
| I band proteins |
|
|
| Actin |
Lethality (cardiac  -actin:
Kumar |
Actin and nemaline myopathies |
|
et al. 1997) |
(skeletal muscle -actin:
Nowak et al. |
|
|
1999, Ilkovski et al. 2001); |
|
|
dilated cardiomyopathy (cardiac |
|
|
-actin:
Olson et al. 1998); |
|
|
hypertrophic cardiomyopathy (cardiac |
|
|
-actin:
Olson et al. 2000) |
| Tropomyosin |
Cardiac hypertrophy and lethality |
Hypertrophic cardiomyopathy |
|
(mouse) (-TM:
Prabhakar et al. 2001); |
(-TM:
Michele & Metzger 2000); |
|
nemaline myopathy (mouse) |
nemaline myopathy (-TM,
ß-TM: |
|
(slow -TM:
Corbett et al. 2001) |
Donner et al. 2002, Michele & |
|
|
Metzger 2000); |
|
|
dilated cardiomyopathy (-TM:
Olson |
|
|
et al. 2001) |
| Troponins |
Cardiomyopathies, myocyte disarray, |
Hypertrophic cardiomyopathy (cardiac |
|
premature death (mouse) (TnT, TnI: |
TnT, TnI, TnC: Hoffman et al. 2001, |
|
Maass & Leinwand 2000, Dalloz |
Marian & Roberts 2001, Seidman
& |
|
et al. 2001) |
Seidman 2001) |
| Tropomodulin |
Dilated cardiomyopathy (mouse) |
Unknown |
|
(E-Tmod: Sussman et al. 1998b) |
|
| CARP |
Levels of CARP  in cardiac |
Unknown |
|
hypertrophy (rat) (Aihara et al 2000) |
|
| Thick filament |
|
|
| and M line |
|
|
| components |
|
|
| Myosin |
Cardiomyopathies, embryonic lethality, |
Hypertrophic cardiomyopathy |
|
myocyte disarray, sudden cardiac |
(MyHC, MLC: Marian & Roberts |
|
death, compromised exercise capacity |
2001, Seidman & Seidman 2001) |
|
(mouse) (
and ß-MyHC); |
|
|
myocyte disarray, cardiac hypertrophy |
|
|
(rabbit) (ß-MyHC) (Maass &
Leinwand |
|
|
2000, Dalloz et al. 2001); |
|
|
skeletal muscle hypertrophy/growth and |
|
|
muscled defects (mouse) (fast skeletal |
|
|
MyHC: Acakpo-Satchivi et al. 1997, |
|
|
Allen et al. 2001); |
|
|
lethality (mouse) (-MyHC:
Jones |
|
|
et al. 1996) |
|
| MyBP-C |
Dilated cardiomyopathy (mouse) |
Hypertrophic cardiomyopathy |
|
(McConnell et al. 1999); |
(Marian & Roberts 2001, |
|
hypertrophic cardiomyopathy and |
Seidman & Seidman 2001) |
|
sudden death, 
exercise capacity |
|
|
(mouse) (Yang et al. 2001, Harris |
|
|
et al. 2002) |
|
| AMP-deaminase |
Unknown |
Skeletal muscle dysfunction and |
|
|
weakness (Morisaki et al. 1992) |
| P94/Calpain 3 |
Decreased grip strength and progressive |
Limb girdle muscular dystrophy |
|
muscular dystrophy (mouse) (Tagawa |
type 2A (Richard et al. 1995) |
|
et al. 2000, Richard et al. 2000) |
|
| Third and fourth |
|
|
| filament systems |
|
|
| Titin |
Cardiac dysfunction (zebrafish) (Xu |
Dilated cardiomyopathy (Gerull |
|
et al. 2002); |
et al. 2002, Itoh-Satoh et al. 2002) |
|
muscular dystrophy with myositis |
|
|
(mouse) (Garvey et al. 2002) |
|
| Nebulin |
Unknown |
Nemaline myopathy (Pelin et al. 1999, |
|
|
Gurgel-Giannetti et al. 2001) |
| Nebulette |
Unknown |
Nonfamilial idiopathic dilated |
|
|
cardiomyopathy (Arimura et al. 2000) |
| Z-line proteins |
|
|
| CRP3/MLP |
Dilated cardiomyopathy (mouse) |
Levels in failing human
myocardium |
|
(Arber et al. 1997) |
(Zolk et al. 2000) |
| ALP |
Right ventricular cardiomyopathy |
Unknown |
|
(mouse) (Pashmforoush et al. 2001) |
|
| Cypher |
Striated muscle failure (mouse) |
Unknown |
|
(Zhou et al. 2001) |
|
| Myotilin |
Unknown |
Limb girdle muscular dystrophy |
|
|
type 1A (Hauser et al. 2000) |
| Telethonin |
Unknown |
Limb girdle muscular dystrophy |
|
|
type 2G (Moreira et al. 2000) |
| Intermediate |
|
|
| filament proteins |
|
|
| Desmin |
Muscle degeneration and cardiomyopathy |
Desmin myopathy with corresponding |
|
(mouse) (Li et al. 1997, Milner et
al. |
cardiac and skeletal myopathies |
|
1999, Balogh et al. 2002) |
(Goebel 1995) |
| Emerin and |
Emery-Dreifuss muscular dystrophy |
Emery-Dreifuss (X-linked and AD |
| Lamins A
and C |
(mouse) (Sullivan et al. 1999); |
forms) and limb girdle muscular |
|
dilated cardiomyopathy (mouse) |
dystrophy type 1B; |
|
(Raharjo et al. 2001) |
dilated cardiomyopathy; lipodystrophy |
|
|
(Emery 2000, Morris 2001) |
| Microtubules |
|
|
|
Unknown |
Aberrant levels and dynamics of |
|
|
microtubules implicated in certain |
|
|
cardiomyopathies (Hein et al. 2000); |
|
|
colchicine skeletal muscle |
|
|
myopathy (Fernandez et al. 2002) |
| Membrane- |
|
|
| associated |
|
|
| proteins |
|
|
| Integrins |
Muscular dystrophy (mouse) |
Congenital myopathy (Hayashi |
|
(7: Mayer
et al. 1997) |
et al. 1998) |
| Dystrophin |
Muscular dystrophy (mouse) |
Duchenne's and Becker's muscular |
|
(Sicinski et al. 1989) |
dystrophy (Hoffman et al. 1987); |
|
|
X-linked dilated cardiomyopathy |
|
|
(Muntoni et al. 1993) |
, ß,
 , and  |
Muscular dystrophy (mouse) (:
Duclos |
Limb girdle muscular dystrophies |
| sarcoglycans |
et al. 1998; :
Hack et al. 1998; ß: Araishi |
(Gordon & Hoffman 2001) |
|
et al. 1999; :
Coral-Vazquez et al. 1999); |
|
|
Muscular dystrophy, dilated or hypertrophic |
|
|
cardiomyopathy (hamster) (:
Nigro et al. |
|
|
1996, Sakamoto et al. 1997, Straub
et al. 1998) |
|
| Plakoglobin/ |
Cardiac muscle rupture; lethality (mouse) |
Naxos disease (Norgett et al. 2000) |
| Desmoplakin |
(Ruiz et al. 1996, Gallicano et al.
2001) |
|
| Plectin |
Lethality; epidermolysis bullosa simple |
EBS-MD (Gache et al. 1996) |
|
muscular dystrophy (EBS-MD) (mouse) |
|
|
(Andra et al. 1997) |
|
|
Biochemistry and Molecular Biology Resources