S. Ortega et al., NEURONAL DEFECTS AND DELAYED WOUND-HEALING IN MICE LACKING FIBROBLASTGROWTH-FACTOR-2, Proceedings of the National Academy of Sciences of the United Statesof America, 95(10), 1998, pp. 5672-5677
Basic fibroblast growth factor (FGF2) is a wide-spectrum mitogenic, an
giogenic, and neurotrophic factor that is expressed at low Bevels in m
any tissues and cell types and reaches high concentrations in brain an
d pituitary, FGF2 has been implicated in a multitude of physiological
and pathological processes, including limb development, angiogenesis,
wound healing, and tumor growth, but its physiological role is still u
nclear, To determine the function of FGF2 in vivo, we have generated F
GF2 knockout mice, lacking ail three FGF2 isoforms, by homologous reco
mbination ire embryonic stem cells. FGF2(-/-) mice are viable, fertile
and phenotypically indistinguishable from FGF2(+/+) littermates by gr
oss examination, However, abnormalities ire the cytoarchitecture of th
e neocortex, most pronounced in the frontal motor-sensory area, can be
detected by histological and immunohistochemical methods. A significa
nt reduction in neuronal density is observed in most layers of the mot
or cortex in the FGF2(-/-) mice, with layer V being the most affected,
Cell density is normal in other regions of the brain such as the stri
atum and the hippocampus. In addition, the healing of excisional skin
wounds is delayed in mice lacking FGF2. These results indicate that FG
F2, although not essential for embryonic development, plays a specific
role in cortical neurogenesis and skin wound healing in mice, which,
in spite of the apparent redundancy of FGF signaling, cannot be carrie
d out by other FGF family members.