CENTROMERE PROTEIN-B NULL MICE ARE MITOTICALLY AND MEIOTICALLY NORMALBUT HAVE LOWER-BODY AND TESTIS WEIGHTS

CENP-B is a constitutive centromere DNA-binding protein that is conser ved in a number of mammalian species and in yeast. Despite this conser vation, earlier cytological and indirect experimental studies have pro vided conflicting evidence concerning the role of this protein in mito sis. The requirement of this protein in meiosis has also not previousl y been described. To resolve these uncertainties, we used targeted dis ruption of the Cenpb gene in mouse to study the functional significanc e of this protein in mitosis and meiosis. Male and female Cenpb null m ice have normal body weights at birth and at weaning, but these subseq uently lag behind those of the heterozygous and wild-type animals. The weight and sperm content of the testes of Cenpb null mice are also si gnificantly decreased. Otherwise, the animals appear developmentally a nd reproductively normal. Cytogenetic fluorescence-activated cell sort ing and histological analyses of somatic and germline tissues revealed no abnormality. These results indicate that Cenpb is not essential fo r mitosis or meiosis, although the observed weight reduction raises th e possibility that Cenpb deficiency may subtly affect some aspects of centromere assembly and function, and result in reduced rate of cell c ycle progression, efficiency of microtubule capture, and/or chromosome movement. A model for a functional redundancy of this protein is pres ented.