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

Authors

    • Anatomisches InstitutUniversität Bonn
  • Heinrich Büssow
    • Anatomisches InstitutUniversität Bonn
  • Kevin L. Seburn
    • The Jackson Laboratory
  • Gregory A. Cox
    • The Jackson Laboratory
  • Diane McVey Ward
    • Department of PathologyUniversity of Utah School of Medicine
  • Jerry Kaplan
    • Department of PathologyUniversity of Utah School of Medicine
  • Thomas Franz
    • Anatomisches InstitutUniversität Bonn
Original Contributions

DOI: 10.1007/s00335-005-0015-1

Cite this article as:
Runkel, F., Büssow, H., Seburn, K.L. et al. Mamm Genome (2006) 17: 203. doi:10.1007/s00335-005-0015-1

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.

Copyright information

© Springer Science+Business Media Inc. 2006