Table 2.
Phenotypes of Null and Tissue-Specific Fgf Mutations
| Gene Name | Viability /Age at Death of Null Mutant | Null Phenotype (Organ, Structure, or Cell Type Affected) | Tissue-Specific (Conditional) Phenotypes, Redundant Phenotypes, Phenotypes Induced by Physiological Challenge | Selected References |
|---|---|---|---|---|
| (a) Phenotypes of germline and conditional loss-of-function Fgf mutations in mice | ||||
| Fgf1 | Viable | No apparent phenotype | An aggressive diabetic phenotype with white adipocyte remodeling on high-fat diet | 3,4 |
| Fgf2 | Viable | Cortical neuron, vascular smooth muscle, blood pressure, skeletal development, and wound healing | Decreased cardiac hypertrophy induced by ischemic injury and delayed wound healing; Increased bone mineralization in high molecular weight isoform knockout | 5–11 |
| Fgf3 | Viable | Inner ear and skeletal development | Heart development (redundant with Fgf10) | 12,13 |
| Fgf4 | E4-5 | Blastocyst inner cell mass | Limb bud development (redundant with Fgf8) | 14–17 |
| Fgf5 | Viable | Hair follicle development | 18 | |
| Fgf6 | Viable | Muscle development | Muscle regeneration | 19–21 |
| Fgf7 | Viable | Hair follicle and ureteric bud development and synaptogenesis | Thymus regeneration (radiation injury) and wound healing | 22–26 |
| Fgf8 | E7 | Gastrulation | Heart field, limb, somitogenesis, kidney, CNS, inner ear development, spermatogenesis | 27–39 |
| Fgf9 | P0 | Lung, heart, skeletal, gonad, inner ear, and intestine development | Migration of cerebellar granule neurons and kidney agenesis (redundant with Fgf20) | 40–53 |
| Fgf10 | P0 | Limb bud, lung bud, trachea, thymus, pancreas, pituitary, palate, tongue epithelium, cecum, kidney, submandibular, salivary, lacrimal, and mammary gland, heart, stomach, and white adipose tissue | Lung branching morphogenesis and inner ear development (redundant with Fgf3) | 54–68 |
| Fgf11 | Viable | No identified phenotype | (unpublished) | |
| Fgf12 | Viable | No identified phenotype | Severe ataxia and motor weakness (redundant with Fgf14) | 69 |
| Fgf13 | Viable | Neuronal migration, learning and memory deficits, and microtubule binding | 69–73 | |
| Fgf14 | Viable | Ataxia, motor weakness, learning and memory deficits, and impaired neuronal excitability | Severe ataxia and motor weakness (redundant with Fgf12) | 69,74 |
| Fgf15 | E13.5-P7 | Cardiac outflow tract development, neurogenesis, and bile acid metabolism | Liver regeneration | 75–80 |
| Fgf16 | Viable | Heart development | Promotes cardiac remodeling induced by angiotensin II | 81–83 |
| Fgf17 | Viable | Cerebellum and frontal cortex development | 31,84 | |
| Fgf18 | P0 | CNS, skeletal, palate, and lung development | 40,85–89 | |
| Fgf20 | Viable | Guards hair, teeth, cochlea, and kidney development | Kidney agenesis (redundant with Fgf9) | 40,90–92 |
| Fgf21 | Viable | Energy/lipid metabolism | 75,93,94 | |
| Fgf22 | Viable | Synaptogenesis | Decreased skin papillomas formation following carcinogenesis challenge | 22,95–97 |
| Fgf23 | PW4-13 | Phosphate and vitamin D homeostasis, deafness, middle ear development | 98–102 | |
| (b) Phenotypes of germline and conditional loss-of-function Fgfr mutations in mice | ||||
| Fgfr1 | E7.5-9.5 | Gastrulation, Blastocyst inner cell mass | Hematopoietic cell engraftment | 39,103–114 |
| Osteoblast maturation | ||||
| Limb bud development | ||||
| Hippocampal progenitor cell proliferation | ||||
| Inner ear sensory epithelium | ||||
| Deletion of Ig domain 1 (defect in node regression) | ||||
| Adipocyte metabolism | ||||
| Endothelial Tgfβ expression and endothelial-mesenchymal transition; Endothelial regulation of CXCR4 in liver regeneration and fibrosis | ||||
| Spermatogenesis | ||||
| Fgfr2 | E10-11 | Placenta, no limb buds | Skeletal, lung, limb bud, CNS, GI tract, skin, and adrenal cortex development in Fgfr2b null mice | 115–119 |
| Fgfr1/2 | Myelin sheath thickness in oligodendrocyte | 120–126 | ||
| Kidney, metanephric mesenchyme, ureteric bud, ocular gland development | ||||
| Angiogenesis, vascular integrity | ||||
| Hepato-cytoprotective through regulation of cytochrome P450 enzymes | ||||
| Fgfr3 | Viable | Skeletal overgrowth, inner ear, brain, articular cartilage, oligodendrocyte differentiation, pancreatic growth, intestinal crypt cell growth arrest | Alveolar septation and elastogenesis (redundant with Fgfr4) | 10,127–139 |
| Fgfr4 | Viable | Cholesterol metabolism and bile acid synthesis | Increased liver injury and fibrosis induced by carbon tetrachloride | 131,139–146 |
| Alveolar septation and elastogenesis (redundant with Fgfr3) | ||||
| Vitamin D homeostasis (redundant with Fgfr3) | ||||
| Phosphate homeostasis (redundant with Fgfr1) | ||||
| Fgfrl1 | P0 | Kidney, diaphragm, skeleton | 147,148 | |