How do mutations in lamins A and C cause disease?
Mutations in lamins A and C, nuclear intermediate-filament proteins in nearly all somatic cells, cause a variety of diseases that primarily affect striated muscle, adipocytes, or peripheral nerves or cause features of premature aging. Two new studies (see the related articles beginning on pages 357 and 370) use lamin A/C-deficient mice, which develop striated muscle disease, as a model to investigate pathogenic mechanisms. These reports provide evidence for a stepwise process in which mechanically stressed cells first develop chromatin and nuclear envelope damage and then develop secondary alterations in the transcriptional activation of genes in adaptive and protective pathways.
Worman
Howard J
HJ
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. hjw14@columbia.edu
Courvalin
Jean-Claude
JC
D017398:Alternative Splicing; D002462:Cell Membrane / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D034904:Lamin Type A / Q000235:genetics* / Q000378:metabolism; D032342:Muscle Cells / Q000378:metabolism
D034904:Lamin Type A