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An Adenosine Triphosphatase of the Sucrose Nonfermenting 2 Family, Androgen Receptor-Interacting Protein 4, Is Essential for Mouse Embryonic Development and Cell Proliferation
- Source :
- Molecular Endocrinology. 21:1430-1442
- Publication Year :
- 2007
- Publisher :
- The Endocrine Society, 2007.
-
Abstract
- An adenosine triphosphatase of the sucrose nonfermenting 2 protein family, androgen receptor-interacting protein 4 (ARIP4), modulates androgen receptor activity. To elucidate receptor-dependent and -independent functions of ARIP4, we have analyzed Arip4 gene-targeted mice. Heterozygous Arip4 mutants were normal. Arip4 is expressed mainly in the neural tube and limb buds during early embryonic development. Arip4-/- embryos were abnormal already at embryonic d 9.5 (E9.5) and died by E11.5. At E9.5 and E10.5, almost all major tissues of Arip4-null embryos were proportionally smaller than those of wild-type embryos, and the neural tube was shrunk in some Arip4-/- embryos. Dramatically reduced cell proliferation and increased apoptosis were observed in E9.5 and E10.5 Arip4-null embryos. Mouse embryonic fibroblasts (MEFs) isolated from Arip4-/- embryos ceased to grow after two to three passages and exhibited increased apoptosis and decreased DNA synthesis compared with wild-type MEFs. Comparison of gene expression profiles of Arip4-/- and wild-type MEFs at E9.5 revealed that putative ARIP4 target genes are involved in cell growth and proliferation, apoptosis, cell death, DNA replication and repair, and development. Collectively, ARIP4 plays an essential role in mouse embryonic development and cell proliferation, and it appears to coordinate multiple essential biological processes, possibly through a complex chromatin remodeling system.
- Subjects :
- Male
Sucrose
medicine.medical_specialty
Programmed cell death
Embryonic Development
Biology
Chromatin remodeling
Mice
03 medical and health sciences
0302 clinical medicine
Endocrinology
Internal medicine
medicine
Animals
Molecular Biology
Alleles
Cell Proliferation
030304 developmental biology
Adenosine Triphosphatases
0303 health sciences
DNA synthesis
Reverse Transcriptase Polymerase Chain Reaction
Cell growth
Embryogenesis
DNA Helicases
Gene Expression Regulation, Developmental
General Medicine
Fibroblasts
Embryo, Mammalian
Embryonic stem cell
Cell biology
Androgen receptor
Apoptosis
embryonic structures
Female
Gene Deletion
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 19449917 and 08888809
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Molecular Endocrinology
- Accession number :
- edsair.doi.dedup.....23c7c3d24eab34eb4f584eec1f36053e