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 Lyst(bg-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 Lyst(bg-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 (Lyst(bg)) showed that double heterozygotes 
(Lyst(bg)/Lyst(bg-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 
Lyst(bg-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 Lyst(bg-grey) 
mutation causes instability of the LYST protein. Because the phenotype of 
Lyst(bg) and Lyst(bg-grey) mutants is indistinguishable, at least with respect 
to melanosomes and secretory granules in mast cells, the Lyst(bg-grey) mutation 
defines a critical region for the stability of the murine LYST protein.