Basic Information
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Description
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- FGFR4 (Fibroblast Growth Factor Receptor 4), is a member of the FGFR family of receptor tyrosine kinases. This family regulates a host of cellular functions including angiogenesis, mitogenesis, osteogenesis, myogenesis, carcinogenesis, cellular differentiation, and tissue repair after injury. The FGFR4 protein is a tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation, migration, and in the regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism, and phosphate homeostasis. FGFR4 is required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. FGFR4 plays a role in postnatal lung development and may be involved in the development of skeletal muscle cell lineages.
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Targeting strategy
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Gene targeting strategy for B-hFGFR4 mice. The exons 2-9 of mouse Fgfr4 gene that encode signal peptide and extracellular domain are replaced by human counterparts in B-hFGFR4 mice. The genomic region of mouse Fgfr4 gene that encodes transmembrane domain and cytoplasmic portion is retained. The promoter, 5’UTR and 3’UTR region of the mouse gene are also retained. The chimeric FGFR4 expression is driven by endogenous mouse Fgfr4 promoter, while mouse Fgfr4 gene transcription and translation will be disrupted.
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Protein expression analysis
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Western blot analysis of FGFR4 protein expression in homozygous B-hFGFR4 mice. Various tissue lysates were collected from wild-type C57BL/6N mice (+/+) and homozygous B-hFGFR4 mice (H/H), and then analyzed by western blot with anti-FGFR4 antibody(Santa Cruz, sc-136988). 40 μg total proteins were loaded for western blotting analysis. FGFR4 was detectable in liver, lung, kidney, stomach, small intestine and testis.
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mRNA expression analysis
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Strain specific analysis of FGFR4 mRNA expression in wild-type C57BL/6N mice and B-hFGFR4 mice by RT-PCR. Liver RNA were isolated from wild-type C57BL/6N mice (+/+) and homozygous B-hFGFR4 mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human FGFR4 primers. Mouse Fgfr4 mRNA were detectable only in wild-type C57BL/6 mice. Human FGFR4 mRNA was detectable only in homozygous B-hFGFR4 mice but not in wild-type mice.
