Fibroblast growth factor receptor 1-IIIb is dispensable for skin morphogenesis and wound healing.
Alternative splicing in the extracellular domain is a characteristic feature of members of the fibroblast growth factor receptor (FGFR) family. This splicing event generates receptor variants, which differ in their ligand binding specificities. A poorly characterized splice variant is FGFR1-IIIb, recently found to be a functional FGF receptor predominantly expressed in the skin. Here we show that FGFR1-IIIb is expressed in normal and wounded mouse skin. Reduced expression of this type of receptor was found in wounds of healing-impaired genetically diabetic mice, suggesting that downregulation of FGFR1-IIIb is associated with wound healing defects. To address this possibility, we deleted the IIIb exon of FGFR1 in mice. The lack of FGFR-IIIb did not alter the expression of either FGFR1-IIIc, other FGF receptor genes or of FGFR1-IIIb ligands in normal and wounded skin. Histological analysis of the skin of FGFR1-IIIb knockout animals did not reveal any obvious abnormalities. Furthermore, full-thickness excisional skin wounds in these mice healed normally and no defects could be observed at the macroscopic or histological level. Finally, several genes that encode key players in wound repair were normally expressed in these animals. These data demonstrate that FGFR1-IIIb is dispensable for skin development and wound repair.
Zhang
Hongbing
H
Five Prime Therapeutics Inc., South San Francisco, CA, USA.
Dessimoz
Jessica
J
Beyer
Tobias A
TA
Krampert
Monika
M
Williams
Lewis T
LT
Werner
Sabine
S
Grose
Richard
R
D017398:Alternative Splicing; D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002455:Cell Division; D015536:Down-Regulation; D005091:Exons; D016678:Genome; D006579:Heterozygote; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism / Q000502:physiology*; D012260:Ribonucleases / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014945:Wound Healing
D008024:Ligands; D017468:Receptors, Fibroblast Growth Factor; C496349:Fgfr1 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D012260:Ribonucleases; D001973:Bromodeoxyuridine