Normal spermatogenesis in mice lacking the testis-specific linker histone H1t

H1 histones bind to linker DNA and nucleosome core particles and facilitate the folding of chromatin into a more compact structure. Mammals contain se ven nonallelic subtypes of H1, including testis-specific subtype H1t, which varies considerably in primary sequence from the other H1 subtypes, H1t is found only in pachytene spermatocytes and early, haploid spermatids, const ituting as much as 55% of the linker histone associated with chromatin in t hese cell types. To investigate the role of H1t in spermatogenesis, we disr upted the H1t gene by homologous recombination in mouse embryonic stem cell s. Mice homozygous for the mutation and completely lacking H1t protein in t heir germ cells were fertile and showed no detectable defect in spermatogen esis. Chromatin from H1t-deficient germ cells had a normal ratio of H1 to n ucleosomes, indicating that other H1-subtypes are deposited in chromatin in place of H1t and presumably compensate for most or all H1t functions. The results indicate that despite the unique primary structure and regulated sy nthesis of H1t, it is not essential for proper development of mature, funct ional sperm.