Stanford Home
Ovarian Kaleidoscope Database (OKdb)

Home

History

Transgenic Mouse Models

INFORGRAPHICS

Search
Submit
Update
Chroms
Browse
Admin

Hsueh lab

HPMR

Visits
since 01/2001:
176557

Tumor Necrosis Factor Receptor Superfamily, Member 1a OKDB#: 2183
 Symbols: TNFRSF1A Species: human
 Synonyms: TUMOR NECROSIS FACTOR RECEPTOR 1, TNFR1|TUMOR NECROSIS FACTOR-ALPHA RECEPTOR, TNFAR|TNFR, 55-KD|TNFR, 60-KD  Locus: 12p13.2 in Homo sapiens
HPMR


For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
Mammalian Reproductive Genetics   Endometrium Database Resource   Orthologous Genes   UCSC Genome Browser   GEO Profiles new!   Amazonia (transcriptome data) new!

R-L INTERACTIONS   MGI

DNA Microarrays
SHOW DATA ...
link to BioGPS
General Comment NCBI Summary: The protein encoded by this gene is a member of the TNF-receptor superfamily. This protein is one of the major receptors for the tumor necrosis factor-alpha. This receptor can activate NF-kappaB, mediate apoptosis, and function as a regulator of inflammation. Antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRADD and TRAF2 have been shown to interact with this receptor, and thus play regulatory roles in the signal transduction mediated by the receptor. Germline mutations of the extracellular domains of this receptor were found to be associated with the autosomal dominant periodic fever syndrome. The impaired receptor clearance is thought to be a mechanism of the disease.
General function Receptor, Cell death/survival, Apoptosis
Comment
Cellular localization Plasma membrane
Comment
Ovarian function Follicle development, Oogenesis, Oocyte maturation
Comment Genes whose expression is detected by cDNA array hybridization: GDP/GTP exchangers, GTPase stimulators and inhibitors, apoptosis Rozenn Dalbi?Tran and Pascal Mermilloda Tumor Necrosis Factor (TNF) Receptor Type 2 Is an Important Mediator of TNF alpha Function in the Mouse Ovary. Greenfeld CR et al. It is believed that a finite pool of primordial follicles is established during embryonic and neonatal life. At birth, the mouse ovary consists of clusters of interconnected oocytes surrounded by pregranulosa cells. Shortly after birth, these structures, termed germ cell cysts or nests (GCN), breakdown to facilitate primordial follicle formation. Tumor necrosis factor alpha (TNF) is a widely expressed protein with myriad functions. TNF is expressed in the ovary and may regulate GCN breakdown in rats. We investigated whether it participates in GCN breakdown and follicle formation in mice, utilizing an in vitro ovary culture system, as well as mutant animal models. We found that TNF and both receptors (TNFRSF1A and TNFRSF1B) are expressed in neonatal mouse ovaries, and that TNF promotes oocyte death in neonatal ovaries in vitro. However, deletion of either receptor did not effect follicle endowment, suggesting that TNF does not regulate GCN breakdown in vivo. Tnfrsf1b deletion led to an apparent acceleration of follicular growth, and a concomitant expansion of the primordial follicle population. This expansion of the primordial follicle population does not appear to be due to decreased primordial follicle atresia, though this cannot be ruled out completely. This study demonstrates that mouse oocytes express both TNF receptors and are sensitive to TNF-induced death. Additionally, TNFRSF1B is demonstrated to be an important mediator of TNF function in the mouse ovary, and an important regulator of folliculogenesis.
Expression regulated by
Comment
Ovarian localization Granulosa
Comment Tumor necrosis factor {alpha} (TNF) increases granulosa cell proliferation: dependence on c-Jun and TNF receptor type-1. Son DS, et al . Tumor necrosis factor alpha (TNF) has significant in vitro effects on steroidogenesis and folliculogenesis and reproductive alterations occur in TNF receptor type 1 (TNFR1) knockout mice. The present study investigated the effect of in vitro TNF on granulosa cell proliferation from immature mice at 28 days of age, with emphasis on intracellular signaling that regulates granulosa cell proliferation. TNF dose dependently increased granulosa cell proliferation and the proto-oncogene c-Jun protein. However, other Jun family members such as JunD was expressed constitutively and JunB was not expressed. In vitro TNF did not increase c-Jun and proliferation in granulosa cells from TNFR1 knockout mice. The time course of TNF-induced c-Jun revealed biphasic patterns of short-term (3 h) and long-term (24 h) induction. The time courses of Ser63- and Ser73-phospho c-Jun coincided with changes in total c-Jun. Among MAPK cascades, SAPK/JNK signaling was increased transiently in TNF-treated cells whereas p38MAPK and ERK1 and 2 were not changed. In addition, overexpression of NF-kappaB, and addition of ceramide and 8-Br-cAMP did not increase c-Jun or proliferation. Antisense oligonucleotides for c-Jun blocked cell proliferation induced by TNF. In conclusion, the above results demonstrate that TNF increased c-Jun by activating SAPK/JNK signaling via TNFR1 in mouse granulosa cells and the induced c-Jun resulted in increased cell proliferation.
Follicle stages Preovulatory
Comment This gene was found in a mouse DNA array analysis of transcripts expressed in mouse preovulatory follicles.
Phenotypes
Mutations 0 mutations
Genomic Region show genomic region
Phenotypes and GWAS show phenotypes and GWAS
Links
OMIM (Online Mendelian Inheritance in Man: an excellent source of general gene description and genetic information.)
OMIM \ Animal Model
KEGG Pathways
Recent Publications
None
Search for Antibody


created: Oct. 14, 2003, 10:31 a.m. by: xin   email:
home page:
last update: Nov. 1, 2006, 6:06 a.m. by: hsueh    email:



Use the back button of your browser to return to the Gene List.

Click here to return to gene search form