Strain Detail Sheet

Genetic Alterations:
This is a transgenic, knock-in mouse produced by Heinz Arnheitter.

Genotype Determination:

• 
  
  MMRRC's PCR

ES Cell Line: Not applicable

Phenotype
Coat color is used to determine zygosity and the MMRRC PCR (genotyping assay) is used to confirm transgene integration.

Description of White Spotting mutants

Characteristics of the Mitf Locus:
Microphthalmia (Mitf) locus encodes the basic-helix-loop-helix-leucine zipper protein transcription factor MITF (Microphthalmia associated transcription factor). (9, 26, 27). Tissues/organs that may be affected (depending upon the allele) include pigmentation of the skin, pigmentation and development of the eye and ear, mast cells, osteoclasts, and reproductive cells. Mitf is an important transcription factor that functions to initiate transcription at several other loci within the pigment cell, including tyrosinase (tyr) and tyrosinase-related protein I (TyrpI.) and also regulates Bcl2. In other cell types, for example in osteoclasts and mast cells, Mitf functions as transcription factor of several cell-type specific proteins. There is no evidence that the size of white spots on mice mutant at Mitf are influenced by pheomelanin. However, mice that are both recessive yellow and Mi^wh/+ in genotype are much more eumelanic than mice that are yellow and +/+ (Lamoreux, 1981). Strain background does not appear to influence size or location of spots in mice mutant at Mitf.

Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype

The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.

Mitf^mi-sp/Mitf^mi-sp

        B6.Cg-Mitf<Mi-wh>/Mitf<mi-sp>/J

• pigmentation phenotype
  • pigmentation phenotype (MGI Ref IDs J:12946, J:35685)
    • (MGI Ref ID J:35685)
    • homozygotes have a normal appearance since the mutation is only visibly evident in compound heterozygotes (MGI Ref ID J:12946)
    • the number, kind, and arrangement of cortical pigment granules in the hair is normal (MGI Ref ID J:12946)
    • hypopigmentation (MGI Ref ID J:12946)
      • despite the normal black coat color, homozygotes have reduced tyrosinase activity as evidenced by reduced incorporation of radiolabeled tyrosine into skin slices from 5 day old homozygotes

Mitf^mi-vga9/Mitf^mi-vga9

        involves: C57BL/6 * CBA

• pigmentation phenotype
  • absent coat pigmentation (MGI Ref ID J:89821)
    • white coat
• vision/eye phenotype
  • microphthalmia (MGI Ref ID J:89821)
• integument phenotype
  • absent coat pigmentation (MGI Ref ID J:89821)
    • white coat

Founder genetic background: C57BL/6J-Mitf^Mi-wh, C57BL/6 x CBA

Strain genetic background: C57BL/6

Strain Development: The mice were backcross to C57BL/6 approximately seven generations, followed by intercrossing for approximately four generations. In January 2003 they were backcrossed using B6-mi*sp and this backcrossing continued to the mice that were shipped to MMRRC in 2004.

Suggested Control Mice:

• Wildtype littermates

• Pigmentation
• Neural Crest Development
• Cell Survival
• Development of Eye
• Deafness
• Peristalsis
• Mast Cells
• Osteoclasts
• Reproductive Cells
• Transcription Factors
• Important Regulatory Molecular

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

Primary Reference:

• Hemesath TJ, Steingrimsson E, McGill G, Hansen MJ, Vaught J, Hodgkinson CA, Arnheiter H, Copeland NG, Jenkins NA, Fisher DE. microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family. Genes Dev. 1994 Nov 15;8(22):2770-80. (Medline PMID: 7958932 )
• Steingrimsson E, Moore KJ, Lamoreux ML, Ferre-D'Amare AR, Burley SK, Zimring DC, Skow LC, Hodgkinson CA, Arnheiter H, Copeland NG. Molecular basis of mouse microphthalmia (mi) mutations helps explain their developmental and phenotypic consequences. Nat Genet. 1994 Nov;8(3):256-63. (Medline PMID: 7874168)
• Tachibana M, Perez-Jurado LA, Nakayama A, Hodgkinson CA, Li X, Schneider M, Miki T, Fex J, Francke U, Arnheiter H. Cloning of MITF, the human homolog of the mouse microphthalmia gene and assignment to chromosome 3p14.1-p12.3. Hum Mol Genet. 1994 Apr;3(4):553-7. (Medline PMID: 8069297)

Coat color: See photo and strain description

Other:

MMRRC Breeding System: Sib mating

Breeding Scheme(s):

• Wildtype littermate female x Heterozygous male
• Heterozygous female x Wildtype littermate male

Generation: N>10

Overall Breeding Performance: Good

Average litter size: 6

Recommended wean age: 3 - 4 weeks

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@missouri.edu.