Skinbase

Epidermal Growth Factor Receptor (Egfr), Chr. 11, 9.0 cM, Genome Coordinates: 16647773-16809479

There are two spontaneous mutations of epidermal growth factor receptor, alleles of waved-2 (Egfrwa2, Egfrwa2), 3 chemically induced (EgfrDsk5, EgfrVel, and Egfrwa5), and 5 targeted alleles (EgfrtmArge, Egfrtm1Mag, Egfrtm1Rdk, Egfrtm1Wag, and Egfrtm2(EGFR)Wag). The waved-2 alleles were discovered once the Tgf null demonstrated that it was the gene mutated in the waved-1 mutation. Since Egfr is the receptor for Tgf, this was a likely candidate gene for the phenotypic mimic waved-2. Both mutant mice are normal except for wavy hair. Those on the C3H background also have retinal degeneration in those homozygous for rd1, which is sometimes misinterpreted to be part of this mutant phenotype. Null mutations of Egfr express a variety of phenotypes depending upon their genetic background.

Kashles O; Yarden Y; Fischer R; Ullrich A; Schlessinger J, A dominant negative mutation suppresses the function of normal epidermal growth factor receptors by heterodimerization., Mol Cell Biol 1991 Mar;11(3):1454-63

Warburton D; Seth R; Shum L; Horcher PG; Hall FL; Werb Z; Slavkin HC, Epigenetic role of epidermal growth factor expression and signalling in embryonic mouse lung morphogenesis., Dev Biol 1992 Jan;149(1):123-33

Wiley LM; Wu JX; Harari I; Adamson ED, Epidermal growth factor receptor mRNA and protein increase after the four-cell preimplantation stage in murine development., Dev Biol 1992 Feb;149(2):247-60

Joh T; Darland T; Samuels M; Wu JX; Adamson ED, Regulation of epidermal growth factor receptor gene expression in murine embryonal carcinoma cells., Cell Growth Differ 1992 May;3(5):315-25

Dardik A; Smith RM; Schultz RM, Colocalization of transforming growth factor-alpha and a functional epidermal growth factor receptor (EGFR) to the inner cell mass and preferential localization of the EGFR on the basolateral surface of the trophectoderm in the mouse blastocyst., Dev Biol 1992 Dec;154(2):396-409

Paria BC; Das SK; Andrews GK; Dey SK, Expression of the epidermal growth factor receptor gene is regulated in mouse blastocysts during delayed implantation., Proc Natl Acad Sci U S A 1993 Jan 1;90(1):55-9

Brunet CL; Sharpe PM; Ferguson MW, The distribution of epidermal growth factor binding sites in the developing mouse palate., Int J Dev Biol 1993 Sep;37(3):451-8

Das SK; Tsukamura H; Paria BC; Andrews GK; Dey SK, Differential expression of epidermal growth factor receptor (EGF-R) gene and regulation of EGF-R bioactivity by progesterone and estrogen in the adult mouse uterus., Endocrinology 1994 Feb;134(2):971-81

Luetteke NC; Phillips HK; Qiu TH; Copeland NG; Earp HS; Jenkins NA; Lee DC, The mouse waved-2 phenotype results from a point mutation in the EGF receptor tyrosine kinase., Genes Dev 1994 Feb 15;8(4):399-413

Guyer CA; Woltjer RL; Coker KJ; Staros JV, Peptide substrate recognition by the epidermal growth factor receptor., Arch Biochem Biophys 1994 Aug 1;312(2):573-8

Fowler KJ; Walker F; Alexander W; Hibbs ML; Nice EC; Bohmer RM; Mann GB; Thumwood C; Maglitto R; Danks JA; Chetty R; Burgess AW; Dunn AR, A mutation in the epidermal growth factor receptor in waved-2 mice has a profound effect on receptor biochemistry that results in impaired lactation., Proc Natl Acad Sci U S A 1995 Feb 28;92(5):1465-9

Orellana SA; Sweeney WE; Neff CD; Avner ED, Epidermal growth factor receptor expression is abnormal in murine polycystic kidney., Kidney Int 1995 Feb;47(2):490-9

Boonstra J; Rijken P; Humbel B; Cremers F; Verkleij A; van Bergen en Henegouwen P, The epidermal growth factor., Cell Biol Int 1995 May;19(5):413-30

Miettinen PJ; Berger JE; Meneses J; Phung Y; Pedersen RA; Werb Z; Derynck R, Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor., Nature 1995 Jul 27;376(6538):337-41

Threadgill DW; Dlugosz AA; Hansen LA; Tennenbaum T; Lichti U; Yee D; LaMantia C; Mourton T; Herrup K; Harris RC; Barnard JA; Yuspa SH; Coffey RJ; Magnuson T, Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype., Science 1995 Jul 14;269(5221):230-4

Wiley LM; Adamson ED; Tsark EC, Epidermal growth factor receptor function in early mammalian development., Bioessays 1995 Oct;17(10):839-46

Murillas R; Larcher F; Conti CJ; Santos M; Ullrich A; Jorcano JL, Expression of a dominant negative mutant of epidermal growth factor receptor in the epidermis of transgenic mice elicits striking alterations in hair follicle development and skin structure., EMBO J 1995 Nov 1;14(21):5216-23

Sweet HO; Davisson MT, Remutations at The Jackson Laboratory (Update to Mouse Genome 1993; 91:862-5 - J16313), Mouse Genome 1995;93(4):1030-4

Tong BJ; Das SK; Threadgill D; Magnuson T; Dey SK, Differential expression of the full-length and truncated forms of the epidermal growth factor receptor in the preimplantation mouse uterus and blastocyst., Endocrinology 1996 Apr;137(4):1492-6

Falck L; Forsberg JG, Immunohistochemical studies on the expression and estrogen dependency of EGF and its receptor and C-fos proto-oncogene in the uterus and vagina of normal and neonatally estrogen-treated mice., Anat Rec 1996 Jul;245(3):459-71

Jaskoll T; Choy HA; Chen H; Melnick M, Developmental expression and CORT-regulation of TGF-beta and EGF receptor mRNA during mouse palatal morphogenesis: correlation between CORT-induced cleft palate and TGF-beta 2 mRNA expression., Teratology 1996 Jul;54(1):34-44

Iamaroon A; Tait B; Diewert VM, Cell proliferation and expression of EGF, TGF-alpha, and EGF receptor in the developing primary palate., J Dent Res 1996 Aug;75(8):1534-9

Riese DJ; Kim ED; Elenius K; Buckley S; Klagsbrun M; Plowman GD; Stern DF, The epidermal growth factor receptor couples transforming growth factor-alpha, heparin-binding epidermal growth factor-like factor, and amphiregulin to Neu, ErbB-3, and ErbB-4., J Biol Chem 1996 Aug 16;271(33):20047-52

Berkowitz EA; Seroogy KB; Schroeder JA; Russell WE; Evans EP; Riedel RF; Phillips HK; Harrison CA; Lee DC; Luetteke NC, Characterization of the mouse transforming growth factor alpha gene: its expression during eyelid development and in waved 1 tissues., Cell Growth Differ 1996 Sep;7(9):1271-82

Wu JX; Adamson ED, Kinase-negative mutant epidermal growth factor receptor (EGFR) expression during embryonal stem cell differentiation favours EGFR-independent lineages., Development 1996 Oct;122(10):3331-42

Wang DZ; Hammond VE; Abud HE; Bertoncello I; McAvoy JW; Bowtell DD, Mutation in Sos1 dominantly enhances a weak allele of the EGFR, demonstrating a requirement for Sos1 in EGFR signaling and development., Genes Dev 1997 Feb 1;11(3):309-20

Helmrath MA; Erwin CR; Warner BW, A defective EGF-receptor in waved-2 mice attenuates intestinal adaptation., J Surg Res 1997 Apr;69(1):76-80

Rani CS; Wang F; Fuior E; Berger A; Wu J; Sturgill TW; Beitner-Johnson D ; LeRoith D ; Varticovski L ; Spiegel S, Divergence in signal transduction pathways of platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) receptors. Involvement of sphingosine 1-phosphate in PDGF but not EGF signaling., J Biol Chem 1997 Apr 18;272(16):10777-83

Hansen LA; Alexander N; Hogan ME; Sundberg JP; Dlugosz A; Threadgill DW ; Magnuson T ; Yuspa SH, Genetically null mice reveal a central role for epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development., Am J Pathol 1997 Jun;150(6):1959-75

Miettinen PJ; Warburton D; Bu D; Zhao JS; Berger JE; Minoo P ; Koivisto T ; Allen L ; Dobbs L ; Werb Z ; Derynck R, Impaired lung branching morphogenesis in the absence of functional EGF receptor., Dev Biol 1997 Jun 15;186(2):224-36

Terada A; Minoura H; Toyoda N, Effects of epidermal growth factor on preimplantation mouse embryos., J Assist Reprod Genet 1997 Aug;14(7):404-11

Yamane A; Mayo ML; Bringas P Jr; Chen L; Huynh M; Thai K; Shum L; Slavkin HC, TGF-alpha, EGF, and their cognate EGF receptor are co-expressed with desmin during embryonic, fetal, and neonatal myogenesis in mouse tongue development., Dev Dyn 1997 Aug;209(4):353-66

DiSandro MJ; Baskin LS; Li YW; Werb Z; Cunha GR, Development and regenerative ability of bladder in the transgenic epidermal growth factor receptor gene knockout mouse., J Urol 1997 Sep;158(3 Pt 2):1058-65

Gresik EW; Kashimata M; Kadoya Y; Mathews R; Minami N; Yamashina S, Expression of epidermal growth factor receptor in fetal mouse submandibular gland detected by a biotinyltyramide-based catalyzed signal amplification method., J Histochem Cytochem 1997 Dec;45(12):1651-7

Sibilia M; Steinbach JP; Stingl L; Aguzzi A; Wagner EF, A strain-independent postnatal neurodegeneration in mice lacking the EGF receptor., EMBO J 1998 Feb 2;17(3):719-31

Richards WG; Sweeney WE; Yoder BK; Wilkinson JE; Woychik RP; Avner ED, Epidermal growth factor receptor activity mediates renal cyst formation in polycystic kidney disease., J Clin Invest 1998 Mar 1;101(5):935-9

Miettinen PJ; Chin JR; Shum L; Slavkin HC; Shuler CF; Derynck R ; Werb Z, Epidermal growth factor receptor function is necessary for normal craniofacial development and palate closure., Nat Genet 1999 May;22(1):69-73

Qu CK; Yu WM; Azzarelli B; Feng GS, Genetic evidence that Shp-2 tyrosine phosphatase is a signal enhancer of the epidermal growth factor receptor in mammals., Proc Natl Acad Sci U S A 1999 Jul 20;96(15):8528-33

Jaskoll T; Melnick M, Submandibular gland morphogenesis: stage-specific expression of TGF-alpha/EGF, IGF, TGF-beta, TNF, and IL-6 signal transduction in normal embryonic mice and the phenotypic effects of TGF-beta2, TGF-beta3, and EGF-r null mutations., Anat Rec 1999 Nov 1;256(3):252-68

Kim H; Muller WJ, The role of the epidermal growth factor receptor family in mammary tumorigenesis and metastasis., Exp Cell Res 1999 Nov 25;253(1):78-87

Keegan BP; Sheflin LG; Spaulding SW, The internalization and endosomal trafficking of the EGF receptor in response to EGF is delayed in the waved-2 mouse liver., Biochem Biophys Res Commun 2000 Jan 27;267(3):881-6

Chen B; Bronson RT; Klaman LD; Hampton TG; Wang JF; Green PJ; Magnuson T; Douglas PS; Morgan JP; Neel BG, Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis., Nat Genet 2000 Mar;24(3):296-9

Miettinen PJ; Huotari M; Koivisto T; Ustinov J; Palgi J; Rasilainen S; Lehtonen E; Keski-Oja J; Otonkoski T, Impaired migration and delayed differentiation of pancreatic islet cells in mice lacking EGF-receptors., Development 2000 Jun;127(12):2617-27

Sibilia M; Fleischmann A; Behrens A; Stingl L; Carroll J; Watt FM; Schlessinger J; Wagner EF, The EGF receptor provides an essential survival signal for SOS-dependent skin tumor development, Cell 2000 Jul 21;102(2):211-20

Gallego MI; Binart N; Robinson GW; Okagaki R; Coschigano KT; Perry J; Kopchick JJ; Oka T; Kelly PA; Hennighausen L, Prolactin, growth hormone, and epidermal growth factor activate Stat5 in different compartments of mammary tissue and exert different and overlapping developmental effects., Dev Biol 2001 Jan 1;229(1):163-75

Roh M; Paterson AJ; Asa SL; Chin E; Kudlow JE, Stage-sensitive blockade of pituitary somatomammotrope development by targeted expression of a dominant negative epidermal growth factor receptor in transgenic mice., Mol Endocrinol 2001 Apr;15(4):600-13

Caric D; Raphael H; Viti J; Feathers A; Wancio D; Lillien L, EGFRs mediate chemotactic migration in the developing telencephalon., Development 2001 Nov;128(21):4203-16

Roberts RB; Min L; Washington MK; Olsen SJ; Settle SH; Coffey RJ; Threadgill DW, Importance of epidermal growth factor receptor signaling in establishment of adenomas and maintenance of carcinomas during intestinal tumorigenesis., Proc Natl Acad Sci U S A 2002 Feb 5;99(3):1521-6

Sun H; Oakley B, Development of anterior gustatory epithelia in the palate and tongue requires epidermal growth factor receptor., Dev Biol 2002 Feb 1;242(1):31-43

Sunnarborg SW; Hinkle CL; Stevenson M; Russell WE; Raska CS; Peschon JJ; Castner BJ; Gerhart MJ; Paxton RJ; Black RA; Lee DC, Tumor necrosis factor-alpha converting enzyme (TACE) regulates epidermal growth factor receptor ligand availability., J Biol Chem 2002 Apr 12;277(15):12838-45

Thaung C; West K; Clark BJ; McKie L; Morgan JE; Arnold K; Nolan PM; Peters J; Hunter AJ; Brown SD; Jackson IJ; Cross SH, Novel ENU-induced eye mutations in the mouse: models for human eye disease., Hum Mol Genet 2002 Apr 1;11(7):755-67

Fujino M; Osumi N; Ninomiya Y; Iseki S; Shibasaki Y; Eto K, Disappearance of epidermal growth factor receptor is essential in the fusion of the nasal epithelium., Anat Sci Int 2003 Mar;78(1):25-35

Sharov AA; Weiner L; Sharova TY; Siebenhaar F; Atoyan R; Reginato AM; McNamara CA; Funa K; Gilchrest BA; Brissette JL; Botchkarev VA, Noggin overexpression inhibits eyelid opening by altering epidermal apoptosis and differentiation., EMBO J 2003 Jun 16;22(12):2992-3003

Zenz R; Scheuch H; Martin P; Frank C; Eferl R; Kenner L; Sibilia M; Wagner EF, c-Jun Regulates Eyelid Closure and Skin Tumor Development through EGFR Signaling., Dev Cell 2003 Jun;4(6):879-89

Mak KK; Chan SY, Epidermal growth factor as a biologic switch in hair growth cycle., J Biol Chem 2003 Jul 11;278(28):26120-6

Tran DD; Russell HR; Sutor SL; van Deursen J; Bram RJ, CAML is required for efficient EGF receptor recycling., Dev Cell 2003 Aug;5(2):245-56

Buerger C; Nagel-Wolfrum K; Kunz C; Wittig I; Butz K; Hoppe-Seyler F; Groner B, Sequence-specific peptide aptamers, interacting with the intracellular domain of the epidermal growth factor receptor, interfere with Stat3 activation and inhibit the growth of tumor cells., J Biol Chem 2003 Sep 26;278(39):37610-21

Cai L; Zhang J; Duan E, Dynamic distribution of epidermal growth factor during mouse embryo peri-implantation., Cytokine 2003 Sep 21;23(6):170-8

Peace BE; Hill KJ; Degen SJ; Waltz SE, Cross-talk between the receptor tyrosine kinases Ron and epidermal growth factor receptor., Exp Cell Res 2003 Oct 1;289(2):317-25

Gillgrass A; Cardiff RD; Sharan N; Kannan S; Muller WJ, Epidermal growth factor receptor-dependent activation of Gab1 is involved in ErbB-2-mediated mammary tumor progression., Oncogene 2003 Dec 11;22(57):9151-5

Du X; Tabeta K; Hoebe K; Liu H; Mann N; Mudd S; Crozat K; Sovath S; Gong X; Beutler B, Velvet, a dominant Egfr mutation that causes wavy hair and defective eyelid development in mice., Genetics 2004 Jan;166(1):331-40

Pedersen MW; Tkach V; Pedersen N; Berezin V; Poulsen HS, Expression of a naturally occurring constitutively active variant of the epidermal growth factor receptor in mouse fibroblasts increases motility., Int J Cancer 2004 Feb 20;108(5):643-53

Lee D; Cross SH; Strunk KE; Morgan JE; Bailey CL; Jackson IJ; Threadgill DW, Wa5 is a novel ENU-induced antimorphic allele of the epidermal growth factor receptor., Mamm Genome 2004 Jul;15(7):525-36

Strunk KE; Amann V; Threadgill DW, Phenotypic variation resulting from a deficiency of epidermal growth factor receptor in mice is caused by extensive genetic heterogeneity that can be genetically and molecularly partitioned., Genetics 2004 Aug;167(4):1821-32

Weston CR; Wong A; Hall JP; Goad ME; Flavell RA; Davis RJ, The c-Jun NH2-terminal kinase is essential for epidermal growth factor expression during epidermal morphogenesis., Proc Natl Acad Sci U S A 2004 Oct 28;101(39):14114-9