Uterine Dysfunction and Genetic Modifiers in Centromere Protein B-deficient Mice
AUTOR(ES)
Fowler, Kerry J.
FONTE
Cold Spring Harbor Laboratory Press
RESUMO
Centromere protein B (CENP-B) binds constitutively to mammalian centromere repeat DNA and is highly conserved between humans and mouse. Cenpb null mice appear normal but have lower body and testis weights. We demonstrate here that testis-weight reduction is seen in male null mice generated on three different genetic backgrounds (denoted R1, W9.5, and C57), whereas body-weight reduction is dependent on the genetic background as well as the gender of the animals. In addition, Cenpb null females show 31%, 33%, and 44% reduced uterine weights on the R1, W9.5, and C57 backgrounds, respectively. Production of “revertant” mice lacking the targeted frameshift mutation but not the other components of the targeting construct corrected these differences, indicating that the observed phenotype is attributable to Cenpb gene disruption rather than a neighbouring gene effect induced by the targeting construct. The R1 and W9.5 Cenpb null females are reproductively competent but show age-dependent reproductive deterioration leading to a complete breakdown at or before 9 months of age. Reproductive dysfunction is much more severe in the C57 background as Cenpb null females are totally incompetent or are capable of producing no more than one litter. These results implicate a further genetic modifier effect on female reproductive performance. Histology of the uterus reveals normal myometrium and endometrium but grossly disrupted luminal and glandular epithelium. Tissue in situ hybridization demonstrates high Cenpb expression in the uterine epithelium of wild-type animals. This study details the first significant phenotype of Cenpb gene disruption and suggests an important role of Cenpb in uterine morphogenesis and function that may have direct implications for human reproductive pathology.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=310504Documentos Relacionados
- Arylsulfatase B-deficient mucopolysaccharidosis in rats.
- Neuropeptide B-deficient mice demonstrate hyperalgesia in response to inflammatory pain
- Resistance of young gelatinase B–deficient mice to experimental autoimmune encephalomyelitis and necrotizing tail lesions
- Compensatory Alterations in the Photochemical Apparatus of a Photoregulatory, Chlorophyll b-Deficient Mutant of Maize 1
- Hierarchical Response of Light Harvesting Chlorophyll-Proteins in a Light-Sensitive Chlorophyll b-Deficient Mutant of Maize 1