Sandy (sdy) is a mouse mutant with diluted pigmentation which recently arose in the DBA/2J strain. Genetic tests indicate it is caused by an autosomal recessive mutation on mouse Chromosome 13 near the cr and Xt genetic loci. This mutation is different genetically and hematologically from previously described mouse pigment mutations with storage pool deficiency (SPD). The sandy mutant has diluted pigmentation in both eyes and fur, is fully viable and has prolonged bleeding times. Platelet serotonin levels are extremely low although ATP dependent acidification activity of platelet organelles appears normal. Also, platelet dense granules are extremely reduced in number when analysed by electron microscopy of unfixed platelets. Platelets have abnormal uptake and flashing of the fluorescent dye mepacrine. Secretion of lysosomal enzymes from kidney and from thrombin-stimulated platelets is depressed 2- and 3-fold, and ceroid pigment is present in kidney. Sandy platelets have a reduced rate of aggregation induced by collagen. The sandy mutant has an unusually severe dense granule defect and thus may be an appropriate model for cases of human Hermansky-Pudlak syndrome with similarly extreme types of SPD. It represents the tenth example of a mouse mutant with simultaneous defects in melanosomes, lysosomes and/or platelet dense granules.

We have examined mice doubly homozygous for both pale ear (ep/ep) and beige (bgJ/bgJ) mutations in order to detect genetic interactions between these 2 loci affecting pigmentation and lysosome physiology. The doubly homozygous mouse has a new pigmentation phenotype consistent with independent effects of ep and bg. The beige (Brandt, Elliott & Swank, 1975) and pale ear (Novak & Swank, 1979)genes have abnormal kidney lysosomal enzyme accumulation caused by defective secretion into urine. No cumulative effect on these functions was observed in the new double mutant phenotype. The new phenotype has giant lysosomes typical of the beige mutation. Unexpectedly, the beige gene corrects the effect of the pale ear on serum lysosomal enzyme concentration. There is also a gene dosage effect of the beige gene on this serum lysosomal enzyme phenotype. The results suggest that the beige and pale ear genes affect the same pathway(s) of lysosome biosynthesis and/or processing. The action of the beige gene may precede that of the pale ear gene in lysosome physiology.

The patch (Ph) locus allele, patch-extended (Phe), has significantly less pigmentation than the original mutation and homozygotes have been known to survive to term. Analysing inter- subspecific F1 hybrids, we were able to demonstrate that Phe is a deletional mutation encompassing the platelet-derived growth factor receptor alpha subunit (Pdgfra). The deletion does not appear to extend into the coding sequence of the Kit gene (a related tyrosine kinase receptor). However, we were able to demonstrate that, while the Kit gene is transcribed, it does not encode a functionally active receptor.