Strain Detail Sheet

Phenotype:
Homozygous mutants have a beige coat color that is mottled with a lighter beige color. This appears to be a true chimerism. The eyes are also chimeric sectors of black pigment and absence of pigment.

Characteristics of the Locus: The albino (Tyr) locus encodes the rate-limiting enzyme for pigmentation, which is TYROSINASSE. The absolute requirement for functional TYROSINASE to catalyze the formation of melanin pigment is illustrated by the phenotypes of mice that lack this locus as a result of deletion, for example mice heterozygous for two overlapping deletions, MMRRC:009964 and MMRRC:009965 in which the albino locus is absent. The mice also lack all melanin pigment. Vertebrates that lack normal tyrosinase are characterized by reduction or absence of pigmentation in the eyes and/or skin. If the reduction of pigmentation is severe, optic nerve development may be abnormal, resulting in blindness. Reduction of melanogenesis may result from failure of normal tyrosinase function caused by its abnormal interaction with other proteins, from defects in its regulatory region, from absence or defect of the structural gene. The series of natural mutations that affect availability of normal tyrosinase function includes mutants of this type. C57BL/6J-Tyr^c-2J/Tyr^c-2J, available at The Jackson Laboratory, lacks tyrosinase activity as a result of point mutation in the structural region of the gene; Acromelanic (MMRRC:000140) may have a similar defect. Extreme dilution (MMRRC:000141) seems to have nearly normal pigmentation in the eyes, but their hair pigmentation is a uniform gray. In dark-eyed-albino (MMRRC:000139) the eye pigmentation is somewhat reduced, but intense, while the hair is unpigmented. Chinchilla mice(MMRRC:000144) are very dark, nearly black. Two of the mutant alleles, chinchilla mottled (MMRRC:000145) and extreme dilution mottled (MMRRC:000142) result in chimerism of hair and eye pigmentation that has been attributed to a rearrangement of the DNA 5kb upstream of the tyrosinase locus. One of the genes that regulates the activity of TYROSINASE is MITF. And there are functional interactions between TYROSINASE and TYROSINASE-RELATED PROTEIN within the pigment cell.

Strain Type: Congenic Spontaneous Mutant

Founder genetic background: c^m mutation on a mixed background at MRC, Harwell.

Strain genetic background: C57BL/6J

Strain Development:
Mutation arose at MRC radiobiology unit in Harwell, England, where they were reported by JRS Phillips in several paragraphs in different issues of Mouse Newsletter. Donor received mice from Dr. JB Whitney, U. Georgia about 1981, at which time the mutation was carried with piebald (Ednrb^s). Donor backcrossed for at least ten generations onto C57BL/6J and removed the piebald gene.

• Pigmentation
• Developmental Biology
• Ophthalmology
• Chimerism
• molecular biology of gene regulation
• tyrosinase

Donor: Dr. ML Lamoreux, Texas A&M University

Primary Reference:

Porter S. Larue L. Mintz B. Mosaicism of tyrosinase-locus transcription and chromatin structure in dark vs. light melanocyte clones of homozygous chinchilla-mottled mice. Developmental Genetics. 12(6):393-402, 1991. (Medline: 1822431)

Porter, Susan D. and Cathy J. Meyer. A distal tyrosinase upstream element stimulates gene expression in neural-crest-derived melanocytes of transgenic mice: position-independent and mosaic expression. Development. 1994 Aug;120(8):2103-11. (Medline: PMID: 7925014)

Deol, M.S. and Truslove, G. M. Nonrandom distribution of unpigmented melanocytes in the retina of chinchilla-mottled mice and its significance. In Proc. XIth Int. Pigm. Cell Conf., Sendai, Japan, 1980 pp. 153-157. (Medline: Not available)

Mouse News Letter, February 1980; Vol. 62, Pg. 52

Molecular Basis of the extreme dilution mottled Mouse Mutation: A COMBINATION OF CODING AND NONCODING GENOMIC ALTERATIONS*. J Biol Chem. 2005 Feb 11;280(6):4817-24. Epub 2004 Nov 30. (Medline PMID: 15572362)

Coat color: Beige, mottled with lighter beige

Other:

MMRRC Breeding System: Sib mating

Breeding Scheme(s):

• Homozygous Female x Homozygous Male

Generation: Unknown

Overall Breeding Performance: Good. Breeding performance is similar to that for C57BL/6J mice although occassional females fail to reproduce.

These mice have been fed using a 9% breeder chow however obesity has been noted in this line and switching to a lower % fat in the diet might improve overall breeding.

* Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item #	Description	Distribution Fee/unit (US $)	Units
000142-MU-RESUS	Resuscitation from cryopreserved material	$1,963.00	litter a
000142-MU-SPERM	Cryopreserved spermatozoa	$424.00	aliquot b

^a The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one breedable mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC repository will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC repository.

^b An aliquot contains sufficient material (volume and concentration) for at least two IVF or several artificial inseminations (based on our procedures). The MMRRC makes no guarantee concerning success of these procedures when performed outside the MMRRC facilities.