A role for A-type nuclear lamins in the homeostasis of striated muscle and the immune system.

摘要

A-type nuclear lamins have been gaining much interest in the past decade due in large part to the identification of numerous human mutations within the LMNA gene that are associated with 11 different tissue-specific diseases---collectively termed laminopathies; notable diseases that these mutations are associated with include muscular dystrophy, dilated cardiomyopathy, and more recently a series of progeroid diseases that resemble premature aging. It has been proposed that A-type lamins play both a structural role in buffering the nucleus from external torsional stresses as well as a gene regulation role whereby lamins act as a scaffold to help localize and assist a subset of tissue-defining factors responsible for gene expression. Lmna-/- mice display multiple tissue defects which most notably include muscular dystrophy, dilated cardiomyopathy, reduced thymus and spleen size, and premature death at 6--8 weeks of age. In this dissertation, I describe my studies on the consequences that are associated with the loss of A-type lamins in striated muscle and the immune system.