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Transgenic Mice Overexpressing OGFr Have Delayed DNA Synthesis and Epithelial Repair
Author(s) -
McLaughlin Patricia J.,
Keiper Cara L.,
Verderame Michael F.,
Zagon Ian S.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.680.9
The Opioid Growth Factor (OGF) interacts with the OGF receptor (OGFr) to form a tonically inhibitory pathway regulating DNA synthesis by upregulating the p16 and/or p21 cyclin‐dependent inhibitory kinases in normal and neoplastic cells and tissues. The OGFr gene is located on chromosome 20q13.3 in humans, a site associated with several autoimmune diseases. Transient elevation of OGFr expression decreases cell proliferation relative to controls. The objective of this study was to examine the effects of a stable OGFr overexpression under in vivo conditions. Transgenic mice overexpressing OGFr under tetracycline regulation (Tg(tet)OGFr) were crossed with rtTA‐K5 in order to overexpress OGFr in epithelium. Gastrointestinal epithelium had 3‐fold more OGF receptors in transgenic mice relative to wildtype (WT) (7 ± 1 fmol/mg protein) in receptor binding assays. DNA synthesis measured by BrdU incorporation was reduced up to 75–200% in the basal epithelium in tongue or skin of transgenic mice. Epithelial wounds of transgenic mice healed significantly slower than in WT mice. These data establish a genetic mouse that overexpresses OGFr in epithelium and demonstrates that overexpression of OGFr has a significant impact on epithelial function, thereby providing a novel model to study the repercussions of elevated OGFr during development and wound healing.