Fibroblast growth factor-2 failed to induce angiogenesis in junctional adhesion molecule-A-deficient mice.
OBJECTIVE
We have previously shown that JAM-A regulates fibroblast growth factor-2 (FGF-2)-induced endothelial cell morphology, proliferation, and migration. Whether JAM-A is involved in FGF-2-induced angiogenesis in vivo is not known. We used JAM-A null mice to conclusively determine the role of JAM-A in FGF-2-induced neovascularization.


RESULTS
We generated JAM-A null (JAM-A(-/-)) mice using gene trap technology. These mice, although viable and fertile, exhibited distorted Mendelian and sex ratios, suggesting partial embryonic lethality. Retinal fluorescein angiogram did not reveal any significant morphological differences in the vasculature of JAM-A(-/-) mice compared with wild-type (JAMA-A(+/+)) littermates. To evaluate the role of JAM-A in angiogenesis, we performed an aortic ring assay. FGF-2-induced microvessel growth was evident in aortic rings from JAM-A(+/+) mice, but FGF-2 failed to induce microvessel sproutings in aortic rings from JAM-A(-/-) mice. In a Matrigel plug assay, a known in vivo model for angiogenesis, we found that FGF-2 induced a robust vessel growth in JAM-A(+/+) mice, whereas FGF-2 failed to induce blood vessel formation in plugs from JAM-A(-/-) mice.


CONCLUSIONS
Our results using JAM-A(-/-) mice presented here conclusively establish an essential role for JAM-A in FGF-2-induced angiogenesis.
Cooke
Vesselina G
VG
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
Naik
Meghna U
MU
Naik
Ulhas P
UP
D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D001808:Blood Vessels / Q000196:embryology; D015815:Cell Adhesion Molecules / Q000172:deficiency* / Q000502:physiology*; D020964:Embryo Loss / Q000209:etiology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D066298:In Vitro Techniques; D062726:Junctional Adhesion Molecules; D008098:Litter Size; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology*; D020033:Protein Isoforms / Q000172:deficiency / Q000502:physiology; D011956:Receptors, Cell Surface / Q000172:deficiency*; D012171:Retinal Vessels / Q000502:physiology; D012744:Sex Ratio
D015815:Cell Adhesion Molecules; C498686:F11r protein, mouse; D062726:Junctional Adhesion Molecules; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D016222:Fibroblast Growth Factor 2