• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. Oct 1990; 126(2): 443–449.
PMCID: PMC1204198

The Molecular Basis of Brown, an Old Mouse Mutation, and of an Induced Revertant to Wild Type

Abstract

The murine b locus encodes the tyrosinase related protein, TRP-1, a putative membrane-bound, copper-containing enzyme having about 40% amino acid identity with tyrosinase. The protein is essential for production of black rather than brown hair pigment. We show that skin of mutant brown mice contains the same amount of TRP-1 mRNA as wild type. On sequencing the coding region of the mutant mRNA we find four nucleotide differences from the wild-type (Black) sequence. Two of these differences result in different amino acid residues encoded by the brown allele. By sequencing the TRP-1 gene from a mouse in which a reversion from brown to Black has been induced by ethylnitrosourea we are able to show that only one of these amino acid changes, which substitutes a tyrosine for a conserved cysteine, is the cause of the brown phenotype. This mutation is adjacent to another cysteine at which, in the analogous position in tyrosinase a mutation results in the albino phenotype. The sequence of the revertant is the first report of DNA sequence of an ethylnitrosourea-induced genetic change in mouse.

Full Text

The Full Text of this article is available as a PDF (1.3M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Copeland NG, Hutchison KW, Jenkins NA. Excision of the DBA ecotropic provirus in dilute coat-color revertants of mice occurs by homologous recombination involving the viral LTRs. Cell. 1983 Jun;33(2):379–387. [PubMed]
  • Coulondre C, Miller JH, Farabaugh PJ, Gilbert W. Molecular basis of base substitution hotspots in Escherichia coli. Nature. 1978 Aug 24;274(5673):775–780. [PubMed]
  • Favor J, Neuhäuser-Klaus A, Ehling UH. Radiation-induced forward and reverse specific locus mutations and dominant cataract mutations in treated strain BALB/c and DBA/2 male mice. Mutat Res. 1987 Mar;177(1):161–169. [PubMed]
  • Gossen JA, de Leeuw WJ, Tan CH, Zwarthoff EC, Berends F, Lohman PH, Knook DL, Vijg J. Efficient rescue of integrated shuttle vectors from transgenic mice: a model for studying mutations in vivo. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7971–7975. [PMC free article] [PubMed]
  • Hearing VJ, Jiménez M. Analysis of mammalian pigmentation at the molecular level. Pigment Cell Res. 1989 Mar-Apr;2(2):75–85. [PubMed]
  • Jackson IJ. A cDNA encoding tyrosinase-related protein maps to the brown locus in mouse. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4392–4396. [PMC free article] [PubMed]
  • Jenkins NA, Copeland NG, Taylor BA, Lee BK. Dilute (d) coat colour mutation of DBA/2J mice is associated with the site of integration of an ecotropic MuLV genome. Nature. 1981 Oct 1;293(5831):370–374. [PubMed]
  • Kwon BS, Haq AK, Pomerantz SH, Halaban R. Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mouse c-albino locus. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7473–7477. [PMC free article] [PubMed]
  • Lehrach H, Diamond D, Wozney JM, Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. [PubMed]
  • Lewis SE, Johnson FM, Skow LC, Popp D, Barnett LB, Popp RA. A mutation in the beta-globin gene detected in the progeny of a female mouse treated with ethylnitrosourea. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5829–5831. [PMC free article] [PubMed]
  • Lovett M, Cheng ZY, Lamela EM, Yokoi T, Epstein CJ. Molecular markers for the agouti coat color locus of the mouse. Genetics. 1987 Apr;115(4):747–754. [PMC free article] [PubMed]
  • Müller G, Ruppert S, Schmid E, Schütz G. Functional analysis of alternatively spliced tyrosinase gene transcripts. EMBO J. 1988 Sep;7(9):2723–2730. [PMC free article] [PubMed]
  • Peters J, Andrews SJ, Loutit JF, Clegg JB. A mouse beta-globin mutant that is an exact model of hemoglobin Rainier in man. Genetics. 1985 Aug;110(4):709–721. [PMC free article] [PubMed]
  • Popp RA, Bailiff EG, Skow LC, Johnson FM, Lewis SE. Analysis of a mouse alpha-globin gene mutation induced by ethylnitrosourea. Genetics. 1983 Sep;105(1):157–167. [PMC free article] [PubMed]
  • Richardson KK, Richardson FC, Crosby RM, Swenberg JA, Skopek TR. DNA base changes and alkylation following in vivo exposure of Escherichia coli to N-methyl-N-nitrosourea or N-ethyl-N-nitrosourea. Proc Natl Acad Sci U S A. 1987 Jan;84(2):344–348. [PMC free article] [PubMed]
  • Ruppert S, Müller G, Kwon B, Schütz G. Multiple transcripts of the mouse tyrosinase gene are generated by alternative splicing. EMBO J. 1988 Sep;7(9):2715–2722. [PMC free article] [PubMed]
  • RUSSELL WL. X-ray-induced mutations in mice. Cold Spring Harb Symp Quant Biol. 1951;16:327–336. [PubMed]
  • Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. [PubMed]
  • Schlager G, Dickie MM. Spontaneous mutations and mutation rates in the house mouse. Genetics. 1967 Oct;57(2):319–330. [PMC free article] [PubMed]
  • Schlager G, Dickie MM. Natural mutation rates in the house mouse. Estimates for five specific loci and dominant mutations. Mutat Res. 1971 Jan;11(1):89–96. [PubMed]
  • Shibahara S, Tomita Y, Sakakura T, Nager C, Chaudhuri B, Müller R. Cloning and expression of cDNA encoding mouse tyrosinase. Nucleic Acids Res. 1986 Mar 25;14(6):2413–2427. [PMC free article] [PubMed]
  • Siracusa LD, Russell LB, Jenkins NA, Copeland NG. Allelic variation within the Emv-15 locus defines genomic sequences closely linked to the agouti locus on mouse chromosome 2. Genetics. 1987 Sep;117(1):85–92. [PMC free article] [PubMed]
  • Yamamoto H, Takeuchi S, Kudo T, Sato C, Takeuchi T. Melanin production in cultured albino melanocytes transfected with mouse tyrosinase cDNA. Jpn J Genet. 1989 Apr;64(2):121–135. [PubMed]
  • Zielenska M, Beranek D, Guttenplan JB. Different mutational profiles induced by N-nitroso-N-ethylurea: effects of dose and error-prone DNA repair and correlations with DNA adducts. Environ Mol Mutagen. 1988;11(4):473–485. [PubMed]

Articles from Genetics are provided here courtesy of Genetics Society of America

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...