Mutation of the SNF2 family member Chd2 affects mouse development and survival.
The chromodomain helicase DNA-binding domain (Chd) proteins belong to the SNF2-like family of ATPases that function in chromatin remodeling and assembly. These proteins are characterized by the presence of tandem chromodomains and are further subdivided based on the presence or absence of additional structural motifs. The Chd1-Chd2 subfamily is distinguished by the presence of a DNA-binding domain that recognizes AT-rich sequence. Currently, there are no reports addressing the function of the Chd2 family member. Embryonic stem cells containing a retroviral gene-trap inserted at the Chd2 locus were utilized to generate mice expressing a Chd2 protein lacking the DNA-binding domain. This mutation in Chd2 resulted in a general growth delay in homozygous mutants late in embryogenesis and in perinatal lethality. Animals heterozygous for the mutation showed decreased neonatal viability and increased susceptibility to non-neoplastic lesions affecting most primary organs. In particular, approximately 85% of the heterozygotes showed gross kidney abnormalities. Our results demonstrate that mutation of Chd2 dramatically affects mammalian development and long-term survival.
Marfella
Concetta G A
CG
Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Ohkawa
Yasuyuki
Y
Coles
Andrew H
AH
Garlick
David S
DS
Jones
Stephen N
SN
Imbalzano
Anthony N
AN
D000818:Animals; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics*; D005317:Fetal Growth Retardation / Q000235:genetics / Q000401:mortality; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D023421:Models, Animal; D009154:Mutation; D016019:Survival Analysis
C489844:Chd1 protein, mouse; C514205:Chd2 protein, mouse; D004268:DNA-Binding Proteins; D004265:DNA Helicases