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Related Experiment Videos

Spatially restricted hypopigmentation associated with an Ednrbs-modifying locus on mouse chromosome 10.

H Rhim1, K J Dunn, A Aronzon

  • 1Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, Maryland 20892-4472 USA.

Genome Research
|January 25, 2000
PubMed
Summary
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Genetic modifiers on mouse chromosome 10 influence white spotting patterns in Ednrb(s) mice. These loci, including k10, interact with signaling pathways to regulate melanocyte development.

Area of Science:

  • Genetics
  • Developmental Biology
  • Mammalian Genetics

Background:

  • White spotting (hypopigmentation) in mice exhibits variable expressivity.
  • Modifier loci significantly impact the phenotypic patterns of hypopigmentation.
  • The endothelin receptor B (Ednrb) gene is crucial for melanocyte development.

Purpose of the Study:

  • To identify and characterize genetic modifier loci affecting white spotting patterns in Ednrb(s) mice.
  • To investigate the role of specific alleles on chromosome 10 in hypopigmentation.
  • To explore the interaction between endothelin and mast cell growth factor signaling pathways in melanocyte development.

Main Methods:

  • Intrasubspecific crosses of Ednrb(s) mice (Mayer and C3HeB/FeJ strains).
  • Intercross analyses to identify and map modifier loci.

Related Experiment Videos

  • Molecular linkage analysis using microsatellite markers.
  • Complementation crosses with known mutant alleles (Mgf(Sl), Kit(WJ-2)).
  • Sequence and genomic analyses of candidate genes.

    • Main Results:

    • A novel modifier locus, k10, was identified on mouse chromosome 10.
    • The k10(Mayer) allele is a recessive modifier of dorsal hypopigmentation.
    • The k10(C3H) allele is semidominant, affecting white forelock phenotype, similar to Waardenburg syndrome.
    • The k10 critical interval cosegregates with mast cell growth factor (Mgf).
    • Genomic differences in Mgf between C3HeB/FeJ and C57BL/6J suggest altered Mgf expression contributes to k10(C3H) phenotype.
    • Synergistic interaction between Endothelin and MGF signaling pathways was confirmed.

    Conclusions:

    • Genetic modifiers on chromosome 10, specifically the k10 locus, play a significant role in regulating white spotting patterns.
    • The k10(C3H) allele's association with a white forelock phenotype suggests a link to mast cell growth factor (Mgf) expression.
    • The Endothelin and MGF signaling pathways interact synergistically to control neural crest-derived melanocyte development in vivo.