Homozygous disruption of the Tip60 gene causes early embryonic lethality. Dev Dyn 2009 Nov;238(11):2912-21
Date
10/21/2009Pubmed ID
19842187Pubmed Central ID
PMC2801416DOI
10.1002/dvdy.22110Scopus ID
2-s2.0-70350743144 (requires institutional sign-in at Scopus site) 99 CitationsAbstract
Tat-interactive protein 60 (Tip60) is a member of the MYST family, proteins of which are related by an atypical histone acetyltransferase (HAT) domain. Although Tip60 has been implicated in cellular activities including DNA repair, apoptosis, and transcriptional regulation, its function during embryonic development is unknown. We ablated the Tip60 gene (Htatip) from the mouse by replacing exons 1-9 with a neomycin resistance cassette. Development and reproduction of wild-type and heterozygous animals were normal. However, homozygous ablation of the Tip60 gene caused embryolethality near the blastocyst stage of development, as evidenced by inability of cells in Tip60-null blastocysts to hatch and survive in culture. Monitoring cell proliferation and death by detecting EdU-substituted DNA and TUNEL labeling revealed suppression of cell proliferation concomitant with increased cell death as Tip60-null cells attempted to hatch from blastocysts. These findings indicate that Tip60 is essential for cellular survival during the blastocyst-gastrula transition of embryogenesis.
Author List
Hu Y, Fisher JB, Koprowski S, McAllister D, Kim MS, Lough JMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Blastocyst
Cell Proliferation
Embryo Loss
Embryo, Mammalian
Exons
Gastrula
Genotype
Heterozygote
Histone Acetyltransferases
Homozygote
Lysine Acetyltransferase 5
Mice
Morula
Trans-Activators
