MICE DEVELOP NORMALLY WITHOUT THE H1(0) LINKER HISTONE

H1 histones bind to the linker DNA between nucleosome core particles a nd facilitate the folding of chromatin into a 30-nm fiber, Mice contai n at least seven nonallelic subtypes of H1, including the somatic vari ants Hla through H1e, the testis-specific variant Hit, and the replace ment linker histone H1(0), H1(0) accumulates in terminally differentia ting cells from many lineages, at about the time when the cells cease dividing. To investigate the role of H1(0) in development, we have dis rupted the single-copy H1(0) gene by homologous recombination in mouse embryonic stem cells. Mice homozygous for the mutation and completely lacking H1(0) mRNA and protein grew and reproduced normally and exhib ited no anatomic or histologic abnormalities. Examination of tissues i n which H1(0) is normally present at high levels also failed to reveal any abnormality in cell division patterns. Chromatin from H1(0)-defic ient animals showed no significant change in the relative proportions of the other ill subtypes or in the stoichiometry between linker histo nes and nucleosomes, suggesting that the other H1 histones can compens ate for the deficiency in H1(0) by occupying sites that normally conta in H1(0). Our results indicate that despite the unique properties and expression pattern of H1(0), its function is dispensable for normal mo use development.