Mammalian Genome

, Volume 17, Issue 3, pp 203–210

Grey, a novel mutation in the murine Lyst gene, causes the beige phenotype by skipping of exon 25

  • Fabian Runkel
  • Heinrich Büssow
  • Kevin L. Seburn
  • Gregory A. Cox
  • Diane McVey Ward
  • Jerry Kaplan
  • Thomas Franz
Original Contributions

Abstract

The murine beige mutant phenotype and the human Chediak-Higashi syndrome are caused by mutations in the murine Lyst (lysosomal trafficking regulator) gene and the human CHS gene, respectively. In this report we have analyzed a novel murine mutant Lyst allele, called Lystbg-grey, that had been found in an ENU mutation screen and named grey because of the grey coat color of affected mice. The phenotype caused by the Lystbg-grey mutation was inherited in a recessive fashion. Melanosomes of melanocytes associated with hair follicles and the choroid layer of the eye, as well as melanosomes in the neural tube-derived pigment epithelium of the retina, were larger and irregularly shaped in homozygous mutants compared with those of wild-type controls. Secretory vesicles in dermal mast cells of the mutant skin were enlarged as well. Test crosses with beige homozygous mutant mice (Lystbg) showed that double heterozygotes (Lystbg/Lystbg-grey) were phenotypically indistinguishable from either homozygous parent, demonstrating that the ENU mutation was an allele of the murine Lyst gene. RT-PCR analyses revealed the skipping of exon 25 in Lystbg-grey mutants, which is predicted to cause a missense D2399E mutation and the loss of the following 77 amino acids encoded by exon 25 but leave the C-terminal end of the protein intact. Analysis of the genomic Lyst locus around exon 25 showed that the splice donor at the end of exon 25 showed a T-to-C transition point mutation. Western blot analysis suggests that the Lystbg-grey mutation causes instability of the LYST protein. Because the phenotype of Lystbg and Lystbg-grey mutants is indistinguishable, at least with respect to melanosomes and secretory granules in mast cells, the Lystbg-grey mutation defines a critical region for the stability of the murine LYST protein.

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Copyright information

© Springer Science+Business Media Inc. 2006

Authors and Affiliations

  • Fabian Runkel
    • 1
  • Heinrich Büssow
    • 1
  • Kevin L. Seburn
    • 2
  • Gregory A. Cox
    • 2
  • Diane McVey Ward
    • 3
  • Jerry Kaplan
    • 3
  • Thomas Franz
    • 1
  1. 1.Anatomisches InstitutUniversität BonnGermany
  2. 2.The Jackson LaboratoryBar HarborUSA
  3. 3.Department of PathologyUniversity of Utah School of MedicineSalt Lake CityUSA

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