Compensation by fibroblast growth factor 1 (FGF1) does not account for the mild phenotypic defects observed in FGF2 null mice.
Fibroblast growth factor 1 (FGF1) and FGF2, the prototypic members of the FGF family of growth factors, have been implicated in a variety of physiological and pathological processes. Unlike most other FGFs, FGF1 and FGF2 are ubiquitously expressed and are not efficiently secreted. Gene knockouts in mice have previously demonstrated a role for FGF2 in brain development, blood pressure regulation, and wound healing. The relatively mild phenotypic defects associated with FGF2 deletion led to the hypothesis that the continued expression of other FGFs partially compensated for the absence of FGF2 in these mice. We now report our generation of mice lacking FGF1 and their use, in combination with our previously described FGF2 null mice, to produce mice lacking both FGF1 and FGF2. FGF1-FGF2 double-knockout mice are viable and fertile and do not display any gross phenotypic defects. In the double-knockout mice we observed defects that were similar in extent to those previously described for the FGF2 null mice. Differences in the organization of neurons of the frontal motor cortex and in the rates of wound healing were observed. We also observed in FGF2(-/-) mice and in FGF1-FGF2 double-knockout mice novel impairments in hematopoiesis that were similar in severity. Essentially no abnormalities were found in mice lacking only FGF1. Our results suggest that the relatively mild defects in FGF2 knockout animals are not a consequence of compensation by FGF1 and suggest highly restricted roles for both factors under normal developmental and physiological conditions.
Miller
D L
DL
Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.
Ortega
S
S
Bashayan
O
O
Basch
R
R
Basilico
C
C
D000818:Animals; D005314:Embryonic and Fetal Development / Q000235:genetics; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout
D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1