Mutants in the mouse NuRD/Mi2 component P66alpha are embryonic lethal.
BACKGROUND
The NuRD/Mi2 chromatin complex is involved in histone modifications and contains a large number of subunits, including the p66 protein. There are two mouse and human p66 paralogs, p66alpha and p66beta. The functions of these genes are not clear, in part because there are no mutants available, except in invertebrate model systems.


METHODS
We made loss of function mutants in the mouse p66alpha gene (mp66alpha, official name Gatad2a, MGI:2384585). We found that mp66alpha is essential for development, as mutant embryos die around day 10 of embryogenesis. The gene is not required for normal blastocyst development or for implantation. The phenotype of mutant embryos and the pattern of gene expression in mutants are consistent with a role of mp66alpha in gene silencing.


CONCLUSIONS
mp66alpha is an essential gene, required for early mouse development. The lethal phenotype supports a role in execution of methylated DNA silencing.
Marino
Susan
S
Howard Hughes Medical Institute, Department of Developmental Biology, Beckman Center, Stanford University School of Medicine, Stanford, California, United States of America.
Nusse
Roel
R
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001755:Blastocyst; D022202:Chromosomes, Artificial, Bacterial; D003001:Cloning, Molecular; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D020868:Gene Silencing; D005804:Genes, Lethal / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012097:Repressor Proteins / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
D015415:Biomarkers; D006657:Histones; D012097:Repressor Proteins; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex