D2 mice aged from 14 days to 1, 4, 8, 11, and 14 months were stimulated with drifting gratings at 100% contrast. None of the D2 animals at any age were able to track the stimuli at any drift speed (1–30 deg/s) or spatial frequency (0.03–0.5 cyc/deg;
n = 28;
Fig. 1). Weak fleeting responses that could not be reproduced were noted occasionally; however, these were not bona fide tracking movements (see the Methods section and
Supplementary Movie S1 for a typical B6 response and
Supplementary Movies S2 and
S3 for typical and atypical D2 behavior). To determine whether this phenotype was strain specific or caused by the specific mutations in
Gpnmb, experiments were repeated in D2-
Gpnmb+ mice, which do not develop high IOP or glaucomatous optic neuropathy.
10 Surprisingly, these mice (
n = 8) also lacked optomotor head-tracking responses, indicating that the D2 phenotype is not affected by Gpnmb loss of function. To rule out effects of both
GpnmbR150X and
Tyrp1b mutations, optomotor responses were assessed in B6.
isaD2ipdD2 mice (see the Methods section). Despite being homozygous for mutations in both genes, these mice had a measurable spatial frequency threshold that was decreased by 17% at 5 months of age compared with age-matched B6 acuity. A small but significant difference (
P < 0.001) was observed between B6.
isaD2ipdD2 males (0.354 ± 0.007,
n = 3) and females (0.264 ± 0.004,
n = 3). No other differences between the sexes were observed for any of the other strains, and although a difference between the sexes for this strain cannot be ruled out, it is probably due to chance. Further analysis of potential sex-related differences may need to be performed on this strain. In addition, photopic spatial frequency thresholds in the first generation from D2 and B6 crosses were significantly higher (
P < 0.001) than in B6 mice, suggesting that recessive D2 alleles underlie the lack of head-tracking behavior in D2 mice. Overall, these results demonstrate that the presence of optomotor reflex in D2 and B6 mouse lines is a strain-specific trait that is not related to the known glaucoma-causing mutations.