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Variable expression of Dkc1 mutations in mice
Author(s) -
He Jun,
Gu Baiwei,
Ge Jingping,
Mochizuki Yuko,
Bessler Monica,
Mason Philip J.
Publication year - 2009
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.20509
Subject(s) - biology , mutation , dyskeratosis congenita , mutant , allele , genetics , gene , variable expression , bone marrow failure , cancer research , haematopoiesis , telomere , stem cell
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 inmice, as in humans. genesis 47:366–373, 2009. © 2009 Wiley‐Liss, Inc.