α-chimaerin (α-chimerin), a Rac-specific GTPase activating protein, plays a key role to wire neurons precisely in the brain. Indeed, miffy mice, α-chimaerin spontaneous null mutant mice, have abnormal midline crossing of corticospinal tract axons and abnormal spinal central pattern generators, resulting in exhibiting a rabbit hopping gait (Iwasato, 2007). A more recent study reported that when α2-chimaerin, one of two major isoforms of α-chimaerin and known as a gene causing Duane Retraction Syndrome, was knocked-down in neurons in oculomotor nuclei, its axon guidance was impaired in zebrafish (Clark, 2013). Here we found that miffy mice were significantly less sensitive to pilocarpine which induces myosis. Instillation of 1% pilocarpine hydrochloride into the eye shrank the pupil by 80% in wild-type mice, whereas miffy mice exhibited less than 40% shrinking of the pupil. The pupillary response to light occurred in miffy mice but the time course of the size change of the pupil was altered compared to wild-type mice. In addition, the effect of atropine to induce mydriasis seemed more profound in miffy mice than in wild-type mice.
Myosis is controlled by parasympathetic nerves innervating to sphincter muscles of the pupil, originated from oculomotor nuclei through ciliary ganglion, and mydriasis is controlled by sympathetic nerves. Our current results suggest that lacking of α-chimaerin altered mechanisms balanced by sympathetic and parasympathetic nerves to regulate the pupil size.