Abstract
Albinism, due to a lack of melanin pigment, is one of the oldest known mutations in mice. Tyrosinase (monophenol oxygenase, EC 1.14.18.1) is the first enzyme in the pathway for melanin synthesis, and the gene encoding this enzyme has been mapped to the mouse albino (c) locus. We have used mouse tyrosinase cDNA clones and genomic sequencing to study the albino mutation in laboratory mice. Within the tyrosinase gene coding sequences, a G to C transversion at nucleotide 308, causing a cysteine to serine mutation at amino acid 103, is sufficient to abrogate pigment production in transgenic mice. This same base pair change is fully conserved in classical albino strains of laboratory mice. These results indicate that a conserved mutation in the tyrosinase coding sequences is responsible for the classical albino mutation in laboratory mice, and also that most albino laboratory mouse strains have been derived from a common ancestor.
MeSH Terms
Albinism/enzymology,genetics
Animals
Base Sequence
Blotting, Southern
Cloning, Molecular
Cysteine
Female
Male
Melanins/metabolism
Mice
Mice, Transgenic
Molecular Sequence Data
Monophenol Monooxygenase/genetics
Mutation
Restriction Mapping
Serine
Chemicals
Melanins
Serine
Monophenol Monooxygenase
Cysteine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Yokoyama T
Howard Hughes Medical Institute, Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030.
Silversides D W
Waymire K G
Kwon B S
Takeuchi T
Overbeek P A
References (13)
13 references, click to expand
-
Analysis of the albino-locus region of the mouse: IV. Characterization of 34 deficiencies.
Genetics. 1982 Mar;100(3):427-53
PMID: 7117820
-
"A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum.
Anal Biochem. 1984 Feb;137(1):266-7
PMID: 6329026
-
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):7473-7
PMID: 2823263
-
Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase.
Science. 1988 Jan 29;239(4839):487-91
PMID: 2448875
-
Sequence analysis of mouse tyrosinase cDNA and the effect of melanotropin on its gene expression.
Biochem Biophys Res Commun. 1988 Jun 30;153(3):1301-9
PMID: 3134020
-
Functional analysis of alternatively spliced tyrosinase gene transcripts.
EMBO J. 1988 Sep;7(9):2723-30
PMID: 3141148
-
Identification of the albino mutation of mouse tyrosinase by analysis of an in vitro revertant.
Proc Natl Acad Sci U S A. 1990 Sep;87(18):7010-4
PMID: 2119500
-
Isolation, chromosomal mapping, and expression of the mouse tyrosinase gene.
J Invest Dermatol. 1989 Nov;93(5):589-94
PMID: 2507645
-
Melanin production in cultured albino melanocytes transfected with mouse tyrosinase cDNA.
Jpn J Genet. 1989 Apr;64(2):121-35
PMID: 2517217
-
A point mutation in the tyrosinase gene of BALB/c albino mouse causing the cysteine----serine substitution at position 85.
Eur J Biochem. 1990 Apr 30;189(2):455-61
PMID: 2110899
-
Melanization in albino mice transformed by introducing cloned mouse tyrosinase gene.
Development. 1990 Feb;108(2):223-7
PMID: 2112453
-
Rescue of the albino phenotype by introduction of a functional tyrosinase gene into mice.
EMBO J. 1990 Sep;9(9):2819-26
PMID: 2118105
-
Molecular basis of mouse Himalayan mutation.
Biochem Biophys Res Commun. 1989 May 30;161(1):252-60
PMID: 2567165