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Linda K McLoon, Laura Johnson; Defining a potential molecular basis for infantile nystagmus syndrome using an albino mouse model. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1140.
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© ARVO (1962-2015); The Authors (2016-present)
Infantile nystagmus syndrome (INS) is a gaze-holding disorder characterized by conjugate, uncontrolled oscillation of the eyes that can result in significant loss of visual acuity for most individuals. However, the majority of INS patients have no known contributing factors in the absence of known sensory afferent defects. Using a combinatorial strategy using the albino mouse model of nystagmus, we performed RNAseq on 6 different genotypes of mice based on level of pigmentation in an attempt to discover potential molecular differences that might account for nystagmus.
Oculomotor and abducens cranial motor neurons were dissected en bloc from the following mouse strains: C57BL6, 129S, B6(CG)-Tyr(c-2J)/J, DBA/1J, BALB/c, and CD-1. RNA was isolated using a Qiagen kit, and RNAseq analyses were performed in the Genomics Core at the University of Minnesota. Differential RNA expression levels were compared between the genotypes, and between either C57BL/6 or 129S6 or both and the albino/hypopigmented gene sets to determine expression that was over-expressed or under-expressed in the pigmented versus the albino and/or hypopigmented mouse models of nystagmus.
The differential expression analysis from RNA isolated from oculomotor neurons identified 18 differentially expressed genes in albinos compared to the pigmented mice. A similar comparison for RNA isolated from abducens neurons identified 24 genes differentially expressed. Ingenuity pathway analysis showed differential expression levels in the EIF2 signaling pathway, which is related to response to cellular stress. Relative to disease, the most altered pathways included neurological disorders specifically involving genes that are related to motor control and coordination. When comparisons were made between both expression patterns for both pigmented mice compared to all non- or hypopigmented mice, both serpina3 isoforms and ribosomal protein S18 were differentially expressed, which have been implicated in ALS and ataxia, respectively.
Using this combinatorial strategy, several candidate molecules were identified whose primary functions are in cell cycle control, stress response, and motor control and coordination. How these interact to produce the uncontrolled oscillatory movements of INS are the subject of further study.
This is a 2020 ARVO Annual Meeting abstract.
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