Mice Homozygous for the subtle gray mutation have a moderate platelet storage pool deficiency and have decreased yellow hair pigment, although the black pigment does not appear affected. This is most evident in the juvenile coat of an agouti background mouse, while on a non-agouti (black) background the difference is difficult to discern and is noted by some reduction in the yellow hair pigment in the ear pinnae. Both female and male homozygotes have an intermediate elevated bleed time of 7.5 minutes compared with 2.2 minutes in heterozygous controls and more than 15 minutes in many other platelet storage pool deficiency models. Subtle gray homozygotes also have moderate deficiencies in platelet dense granules including a 20% reduction in dense granules per platelet, decreased platelet serotonin, decreased collagen-stimulated ATP release from platelets, and decreased platelet aggregation (Swank et al., 1996). These deficiencies are mild compared with those of other platelet storage pool deficiency models, with the subtle gray decrease in platelet serotonin being the most mild of any of the 12 models comparatively assessed by Swank et al (1998). No defects were found in the activities of beta-glucuronidase or beta-galactosidase, lysosomal enzymes of the kidney, distinguishing this from other platelet storage pool disease models such as mocha, muted, light ear, pale ear, palid or pearl (Swank et al., 1996). The subtlety in the dilution of coat color, the shorter bleed time and less severe platelet defects make this a less severe model than other platelet storage pool deficiency models.
The Clcc1m1J spontaneous mutation, which causes increased sensitivity to endoplasmic reticulum stress in the cerebellum, was identified in C3H/HeSnJ (Jia et al., 2015) and has been found homozygous in all C3H/HeSn strains assessed at The Jackson Laboratory, including this mutant subline, which is homozygous for Clcc1m1J.
Subtle gray arose spontaneously in July 1985 in the C3H/HeDiSn-Dscam2J colony at The Jackson Laboratory. The Dscam2J mutation arose spontaneously in 1981 on the C3H/HeDiSn background at The Jackson Laboratory and was maintained by sibling mating until 1983 when hysterectomy rederivation was performed with a homozygous ovarian transplanted female bred to a C3H/HeSnJ male, the progeny of which were maintained by sibling mating. C3H/HeDiSn is approximately equivalent to its more evolved progeny C3H/HeSnJ inbred strain. The subtle gray mutation was cryopreserved on this C3H/HeSnJ background in 1986 when this strain was at generation F3.
|Allele Name||subtle gray|
|Gene Symbol and Name||Slc7a11, solute carrier family 7 (cationic amino acid transporter, y+ system), member 11|
|Strain of Origin||C3H/HeSnJ|
|Molecular Note||Sequencing revealed a large deletion extending from intron 11 through exon 12 and into the intergenic region, creating a new splice site and the replacement of exon 12 with exon 12'. 3' RACE revealed a new stop codon in exon 12' and predicted a modified and truncated protein carboxyl terminus.|