Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The epidermal growth factor receptor (EGFR) and related family members (ERBB2, ERBB3, and ERBB4) previously have been shown to play pivotal roles in the development of female reproductive tissues, in blastocyst implantation, and in placental differentiation. We have cloned and sequenced several naturally occurring alternative transcripts of the human and mouse EGFR genes, which encode novel receptor isoforms containing varying portions of the extracellular ligand-binding domain, but lacking the transmembrane and cytoplasmic domain sequences. The human 1.8-kb and 3-kb alternative EGFR transcripts encode secreted 60-kDa and cell surface-associated 110-kDa EGFR isoforms, respectively. We have developed quantitative ribonuclease protection assays to study the expression of these alternative transcripts in human tissues. Similar to the full-length EGFR mRNAs, the highest expression level of these alternative transcripts occurs in placenta. We speculate that both of these EGFR isoforms may be important regulators of EGF-mediated cell growth and differentiation in human placenta.
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PMID:Characterization and expression of novel 60-kDa and 110-kDa EGFR isoforms in human placenta. 1281 37

Homozygosity for the Egfr(tm1Mag) null allele in mice leads to genetic background dependent placental abnormalities and embryonic lethality. Molecular mechanisms or genetic modifiers that differentiate strains with surviving versus non-surviving Egfr nullizygous embryos have yet to be identified. Egfr transcripts in wildtype placenta were quantified by ribonuclease protection assay (RPA) and the lowest level of Egfr mRNA expression was found to coincide with Egfr(tm1Mag) homozygous lethality. Immunohistochemical analysis of ERBB family receptors, ERBB2, ERBB3, and ERBB4, showed similar expression between Egfr wildtype and null placentas indicating that Egfr null trophoblast do not up-regulate these receptors to compensate for EGFR deficiency. Significantly fewer numbers of bromodeoxyuridine (BrdU) positive trophoblast were observed in Egfr nullizygous placentas and Cdc25a and Myc, genes associated with proliferation, were significantly down-regulated in null placentas. However, strains with both mild and severe placental phenotypes exhibit reduced proliferation suggesting that this defect alone does not account for strain-specific embryonic lethality. Consistent with this hypothesis, intercrosses generating mice null for cell cycle checkpoint genes (Trp53, Rb1, Cdkn1a, Cdkn1b or Cdkn2c) in combination with Egfr deficiency did not increase survival of Egfr nullizygous embryos. Since complete development of the spongiotrophoblast compartment is not required for survival of Egfr nullizygous embryos, reduction of this layer that is commonly observed in Egfr nullizygous placentas likely accounts for the decrease in proliferation.
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PMID:Altered trophoblast proliferation is insufficient to account for placental dysfunction in Egfr null embryos. 1782 58