An absence of both lamin B1 and lamin B2 in keratinocytes has no effect on cell proliferation or the development of skin and hair

Abstract

Nuclear lamins are usually classified as A-type (laminsAand C) or B-type (lamins B1and B2). A-type lamins have been implicated in multiple genetic diseases but are not required for cell growth or development. In contrast, Btype lamins have been considered essential in eukaryotic cells, with crucial roles in DNA replication and in the formation of the mitotic spindle. Knocking down the genes for B-type lamins (LMNB1, LMNB2) in HeLa cells has been reported to cause apoptosis. In the current study, we created conditional knockout alleles for mouse Lmnb1 and Lmnb2, with the goal of testing the hypothesis that B-type lamins are crucial for the growth and viability of mammalian cells in vivo. Using the keratin 14-Cre transgene, we bred mice lacking the expression of both Lmnb1 and Lmnb2 in skin keratinocytes (Lmnb1 δ/ δLmnb2 δ/ δ). Lmnb1 and Lmnb2 transcripts were absent in keratinocytes of Lmnb1 δ/ δLmnb2 δ/ δ mice, and lamin B1 and lamin B2 proteins were undetectable. But despite an absence of B-type lamins in keratinocytes, the skin and hair of Lmnb1 δ/ δLmnb2 δ/ δ mice developednormally and were free of histological abnormalities, even in 2-year-old mice. After an intraperitoneal injection of bromodeoxyuridine (BrdU), similar numbers of BrdU-positive keratinocytes were observed in the skin of wild-type and Lmnb1 δ/ δLmnb2 δ/ δ mice. Lmnb1 δ/ δLmnb2 δ/ δ keratinocytes did not exhibit aneuploidy, and their growth rate was normal in culture. These studies challenge the concept that B-type lamins are essential for proliferation and vitality of eukaryotic cells. © The Author 2011. Published by Oxford University Press. All rights reserved.