title: Variable expression of Dkc1 mutations in mice.
abstract: In humans mutations in DKC1, cause the rare bone marrow failure syndrome dyskeratosis congenita. We have used gene targeting to produce mouse ES cells with Dkc1 mutations that cause DC when in humans. The mutation A353V, the most common human mutation, causes typical DC to very severe DC in humans. Male chimeric mice carrying this mutation do not pass the mutated allele to their offspring. The mutation G402E accounts for a single typical case of DC in a human family. The allele carrying this mutation was transmitted to the offspring with high efficiency. Expression of RNA and protein was reduced compared to wild type animals, but no abnormalities of growth and development or in blood values were found in mutant mice. Thus Dkc1 mutations have variable expression in mice, as in humans.
authors.affiliation: Department of Medicine, Division of Hematology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.forename: Bai-Wei
authors.initials: BW
authors.lastname: Gu
authors.forename: Jingping
authors.initials: J
authors.lastname: Ge
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mochizuki
authors.forename: Monica
authors.initials: M
authors.lastname: Bessler
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mason
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D018797:Cell Cycle Proteins / Q000235:genetics*; D003433:Crosses, Genetic; D019871:Dyskeratosis Congenita / Q000235:genetics / Q000473:pathology; D005260:Female; D005298:Fertility / Q000235:genetics; D015870:Gene Expression; D018390:Gene Targeting / Q000379:methods*; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008136:Longevity / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics*; D013997:Time Factors; D014960:X Chromosome / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; C510431:Dkc1 protein, mouse; D009687:Nuclear Proteins