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Mutations in LMNA, the gene that encodes nuclear lamins A and C, cause up to e ight different diseases collectively referred to as “laminopathies. ”These dis eases affect striated muscle, adipose tissue, peripheral nerve, and bone, or cau se features of premature aging. We investigated the consequences of LMNA mutatio ns on nuclear architecture in skin fibroblasts from 13 patients with different l aminopathies. Western blotting showed that none of the mutations examined led t o a decrease in cellular levels of lamin A or C. Regardless of the disease, we o bserved honeycomb nuclear structures and nuclear envelope blebs in cells examine d by immunofluorescence microscopy. Concentrated foci of lamin A/C in the nucleo plasm were also observed. Only mutations in the head and tail domains of lamins A and C significantly altered the nuclear architecture of patient fibroblasts. T hese results confirm that mutations in lamins A and C may lead to a weakening of a structural support network in the nuclear envelope in fibroblasts and that nu clear architecture changes depend upon the location of the mutation in different domains of lamin A/C.
Mutations in LMNA, the gene that encodes nuclear lamins A and C, cause up to e ight various diseases collectively referred to as “laminopathies.” These dis eases affect striated muscle, adipose tissue, peripheral nerve, and bone, or cau se features premature aging. We investigated the consequences of LMNA mutatio ns on nuclear architecture in skin fibroblasts from 13 patients with different l aminopathies. Western blotting showed that none of the previously examined led toa decrease in cellular levels of lamin A or C. Regardless of the disease , we o bserved honeycomb nuclear structures and nuclear envelope blebs in cells examine d by immunofluorescence microscopy. Concentrated foci of lamin A / C in the nucleo plasm were also observed. Only mutations in the head and tail domains of lamins A and C significantly altered the nuclear architecture of patient fibroblasts. T hese results confirm that mutations in lamins A and C may lead to a weakening of a structural support network i n the nuclear envelope in fibroblasts and that nu clear architecture changes depend upon the location of the mutation in different domains of lamin A / C.