CENP-B is a constitutive centromere DNA-binding protein that is conserved in a number of mammalian species and in yeast. Despite this conservation, earlier cytological and indirect experimental studies have provided conflicting evidence concerning the role of this protein in mitosis. The requirement of this protein in meiosis has also not previously been described. To resolve these uncertainties, we used targeted disruption of the Cenpb gene in mouse to study the functional significance of this protein in mitosis and meiosis. Male and female Cenpb null mice have normal body weights at birth and at weaning, but these subsequently lag behind those of the heterozygous and wild-type animals. The weight and sperm content of the testes of Cenpb null mice are also significantly decreased. Otherwise, the animals appear developmentally and reproductively normal. Cytogenetic fluorescence-activated cell sorting and histological analyses of somatic and germline tissues revealed no abnormality. These results indicate that Cenpb is not essential for mitosis or meiosis, although the observed weight reduction raises the possibility that Cenpb deficiency may subtly affect some aspects of centromere assembly and function, and result in reduced rate of cell cycle progression, efficiency of microtubule capture, and/or chromosome movement. A model for a functional redundancy of this protein is presented.
Testosterone (T) has been shown to be essential for the completion of spermiogenesis. Our previous studies showed that when intratesticular T was suppressed for 11 wk, the conversion of round spermatids between stages VII and VIII of the spermatogenic cycle was markedly suppressed and that elongated spermatids were undetectable. The fate of the round spermatids that did not proceed through this conversion was unclear. The current study aimed to investigate this T-dependent loss of round spermatids during stages VII and VIII. Adult male Sprague-Dawley rats received 24-cm T implants for 1 wk to suppress LH while maintaining spermatogenesis. The T24 implants were removed and replaced with 3-cm T plus 0.4-cm estradiol (TE treatment) to suppress intratesticular T and spermatogenesis, and animals were killed at 0 and 4 days and 1, 2, 3, 4, and 6 wk later. The number of homogenization-resistant elongated spermatids in the testis was counted, and round spermatid populations in stages VII and VIII were quantified using stereological techniques. The hourly production rates (HPR) were calculated, and a ratio was made between the HPR of round spermatids in stages VII and VIII to assess the efficiency of their conversion through these stages. Testicular T levels were suppressed to 2-4% of control values by TE treatment. After 2 wk of TE treatment, the number of homogenization-resistant elongated spermatids was significantly suppressed, falling to < 0.5% of the control value by 6 wk. The HPR of round spermatids in stages VII and VIII was not affected by up to 2 wk of TE treatment, nor was the conversion between these stages interrupted. After 3 wk of TE treatment, the HPR of round spermatids in stages VII and VIII was significantly suppressed, as was the conversion between these stages, the ratio falling to 27% of the control value by 6 wk. In rats treated with TE, histological examination of the cauda epididymidis showed occasional round spermatids after 3 wk of treatment, and large numbers after 6 wk. We conclude that the failure of round spermatids to complete spermiogenesis following T withdrawal is due to stage-specific detachment of round spermatids between stages VII and VIII.
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