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Genetics. Jan 2004; 166(1): 331–340.
PMCID: PMC1470694

Velvet, a dominant Egfr mutation that causes wavy hair and defective eyelid development in mice.


In the course of a large-scale program of ENU mutagenesis, we isolated a dominant mutation, called Velvet. The mutation was found to be uniformly lethal to homozygotes, which do not survive E13.5. Mice heterozygous for the Velvet mutation are born with eyelids open and demonstrate a wavy coat and curly vibrissae. The mutation was mapped to the proximal end of chromosome 11 by genome-wide linkage analysis. On 249 meioses, the locus was confined to a 2.7-Mb region, which included the epidermal growth factor receptor gene (Egfr). An A --> G transition in the Egfr coding region of Velvet mice was identified, causing the amino acid substitution D833G. This substitution alters an essential triad of amino acids (DFG --> GFG) that is normally required for coordination of the ATP substrate. As such, kinase activity is at least mostly abolished, but quaternary structure of the receptor is presumably maintained, accounting for the dominant effect. Velvet is the first known dominant representative of the Egfr allelic series that is fully viable, a fact that makes it particularly useful for developmental studies.

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Selected References

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  • Thaung Caroline, West Katrine, Clark Brian J, McKie Lisa, Morgan Joanne E, Arnold Karen, Nolan Patrick M, Peters Jo, Hunter A Jackie, Brown Steve D M, et al. Novel ENU-induced eye mutations in the mouse: models for human eye disease. Hum Mol Genet. 2002 Apr 1;11(7):755–767. [PubMed]
  • Brown SD, Balling R. Systematic approaches to mouse mutagenesis. Curr Opin Genet Dev. 2001 Jun;11(3):268–273. [PubMed]
  • Brown SD, Peters J. Combining mutagenesis and genomics in the mouse--closing the phenotype gap. Trends Genet. 1996 Nov;12(11):433–435. [PubMed]
  • Carpenter G, Cohen S. Epidermal growth factor. J Biol Chem. 1990 May 15;265(14):7709–7712. [PubMed]
  • Donaldson RW, Cohen S. Epidermal growth factor stimulates tyrosine phosphorylation in the neonatal mouse: association of a M(r) 55,000 substrate with the receptor. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8477–8481. [PMC free article] [PubMed]
  • Ehling UH, Charles DJ, Favor J, Graw J, Kratochvilova J, Neuhäuser-Klaus A, Pretsch W. Induction of gene mutations in mice: the multiple endpoint approach. Mutat Res. 1985 Jun-Jul;150(1-2):393–401. [PubMed]
  • Findlater GS, McDougall RD, Kaufman MH. Eyelid development, fusion and subsequent reopening in the mouse. J Anat. 1993 Aug;183(Pt 1):121–129. [PMC free article] [PubMed]
  • Green MR, Basketter DA, Couchman JR, Rees DA. Distribution and number of epidermal growth factor receptors in skin is related to epithelial cell growth. Dev Biol. 1983 Dec;100(2):506–512. [PubMed]
  • Hrabé de Angelis M, Balling R. Large scale ENU screens in the mouse: genetics meets genomics. Mutat Res. 1998 May 25;400(1-2):25–32. [PubMed]
  • Hrabé de Angelis MH, Flaswinkel H, Fuchs H, Rathkolb B, Soewarto D, Marschall S, Heffner S, Pargent W, Wuensch K, Jung M, et al. Genome-wide, large-scale production of mutant mice by ENU mutagenesis. Nat Genet. 2000 Aug;25(4):444–447. [PubMed]
  • Hubbard SR, Mohammadi M, Schlessinger J. Autoregulatory mechanisms in protein-tyrosine kinases. J Biol Chem. 1998 May 15;273(20):11987–11990. [PubMed]
  • Jhappan C, Stahle C, Harkins RN, Fausto N, Smith GH, Merlino GT. TGF alpha overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas. Cell. 1990 Jun 15;61(6):1137–1146. [PubMed]
  • Jorissen Robert N, Walker Francesca, Pouliot Normand, Garrett Thomas P J, Ward Colin W, Burgess Antony W. Epidermal growth factor receptor: mechanisms of activation and signalling. Exp Cell Res. 2003 Mar 10;284(1):31–53. [PubMed]
  • Juriloff DM, Harris MJ, Banks KG, Mah DG. Gaping lids, gp, a mutation on centromeric chromosome 11 that causes defective eyelid development in mice. Mamm Genome. 2000 Jun;11(6):440–447. [PubMed]
  • Justice MJ, Noveroske JK, Weber JS, Zheng B, Bradley A. Mouse ENU mutagenesis. Hum Mol Genet. 1999;8(10):1955–1963. [PubMed]
  • Klemke RL, Cai S, Giannini AL, Gallagher PJ, de Lanerolle P, Cheresh DA. Regulation of cell motility by mitogen-activated protein kinase. J Cell Biol. 1997 Apr 21;137(2):481–492. [PMC free article] [PubMed]
  • Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, et al. Initial sequencing and analysis of the human genome. Nature. 2001 Feb 15;409(6822):860–921. [PubMed]
  • Li C, Guo H, Xu X, Weinberg W, Deng CX. Fibroblast growth factor receptor 2 (Fgfr2) plays an important role in eyelid and skin formation and patterning. Dev Dyn. 2001 Nov;222(3):471–483. [PubMed]
  • Luetteke NC, Qiu TH, Peiffer RL, Oliver P, Smithies O, Lee DC. TGF alpha deficiency results in hair follicle and eye abnormalities in targeted and waved-1 mice. Cell. 1993 Apr 23;73(2):263–278. [PubMed]
  • 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. [PubMed]
  • Sibilia M, Wagner EF. Strain-dependent epithelial defects in mice lacking the EGF receptor. Science. 1995 Jul 14;269(5221):234–238. [PubMed]
  • Stamos Jennifer, Sliwkowski Mark X, Eigenbrot Charles. Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor. J Biol Chem. 2002 Nov 29;277(48):46265–46272. [PubMed]
  • Stein KF, Norris BE, Mason J. Development of an open eyelid mutant in mus musculus. Dev Biol. 1967 Oct;16(4):315–330. [PubMed]
  • Threadgill DW, Dlugosz AA, Hansen LA, Tennenbaum T, Lichti U, Yee D, LaMantia C, Mourton T, Herrup K, Harris RC, et al. Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. Science. 1995 Jul 14;269(5221):230–234. [PubMed]
  • 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):5216–5223. [PMC free article] [PubMed]
  • Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, et al. The sequence of the human genome. Science. 2001 Feb 16;291(5507):1304–1351. [PubMed]
  • Nolan PM, Peters J, Strivens M, Rogers D, Hagan J, Spurr N, Gray IC, Vizor L, Brooker D, Whitehill E, et al. A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse. Nat Genet. 2000 Aug;25(4):440–443. [PubMed]
  • Wilson AJ, Gibson PR. Role of epidermal growth factor receptor in basal and stimulated colonic epithelial cell migration in vitro. Exp Cell Res. 1999 Jul 10;250(1):187–196. [PubMed]
  • Paria BC, Dey SK. Preimplantation embryo development in vitro: cooperative interactions among embryos and role of growth factors. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4756–4760. [PMC free article] [PubMed]
  • Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001 Feb;2(2):127–137. [PubMed]
  • Yujiri T, Ware M, Widmann C, Oyer R, Russell D, Chan E, Zaitsu Y, Clarke P, Tyler K, Oka Y, et al. MEK kinase 1 gene disruption alters cell migration and c-Jun NH2-terminal kinase regulation but does not cause a measurable defect in NF-kappa B activation. Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7272–7277. [PMC free article] [PubMed]
  • Sandgren EP, Luetteke NC, Palmiter RD, Brinster RL, Lee DC. Overexpression of TGF alpha in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast. Cell. 1990 Jun 15;61(6):1121–1135. [PubMed]
  • Schlessinger Joseph. Ligand-induced, receptor-mediated dimerization and activation of EGF receptor. Cell. 2002 Sep 20;110(6):669–672. [PubMed]

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