AIMS: Muscle LIM protein (MLP) null mice are often used as a model for human 
dilated cardiomyopathy. So far, little is known about the time course and 
pathomechanisms leading to the development of the adult phenotype.
METHODS AND RESULTS: We systematically analysed the contractile phenotype, 
myofilament calcium (Ca(2)(+)) responsiveness, passive myocardial mechanics, 
histology, and mRNA expression in mice aged 4 and 12 weeks. In 4-week-old 
animals, there was no significant difference in the force-frequency relationship 
(FFR) and catecholamine response of intact isolated papillary muscles between 
wild-type (WT) and MLP null myocardium. In 12-week-old animals, WT myocardium 
exhibited a significantly positive FFR, while that of MLP null mice was 
significantly negative, and the inotropic response to catecholamines was 
significantly reduced in MLP null mice. This time course of decline in 
contractile function was confirmed in vivo by echocardiography. Whereas at 4 
weeks of age MLP null mice and WT littermates showed similar levels of SERCA2a 
(sarcoplasmic reticulum Ca(2+) ATPase) expression, the expression was 
significantly lower in 12-week-old MLP null mice compared with littermate 
controls. Myofilament Ca(2)(+) responsiveness was not affected by the lack of 
MLP, irrespective of age. Whereas in 4-week-old animals MLP null myocardium 
showed a trend to an increased compliance compared with the WT, myocardium of 
12-week-old MLP null mice was significantly less compliant than WT myocardium. 
Parallel to the decrease in compliance there was an increase in fibrosis in the 
MLP null animals.
CONCLUSION: Our data suggest that MLP deficiency does not primarily influence 
myocardial contractility. A lack of MLP leads to an age-dependent impairment of 
excitation-contraction coupling with resulting contractile dysfunction and 
secondary fibrosis.