Nystagmus in the B6(CG)Tyr(c-2J)/J Albino Mouse: A Functional and RNAseq Analysis

PURPOSE: Infantile nystagmus syndrome (INS) is a gaze-holding disorder characterized by conjugate, uncontrolled eye oscillations that can result in significant visual acuity loss. INS is often associated with albinism, but the mechanism is unclear. Albino mice have nystagmus; however, a pigmented mouse with a tyr mutation making it phenotypically albino, the B6(CG)-Tyr(c-2J)/J (B6 albino), had not been tested. We tested optokinetic nystagmus reflexes (OKN) in B6 albino and control mice. RNA-Seq was performed on extraocular muscles (EOM), tibialis anterior muscle (TA), abducens (CN6), and oculomotor (CN3) neurons to uncover molecular differences that could account for nystagmus. Two genotypes of mice used are B6(CG)Tyr(c-2J)/J and C57BL/6. The B6(CG)Tyr(c-2J)/J is an albino mouse, C57BL/6 is a pigmented mouse. For each genotype there were four replicated of four types of tissues taken, these tissues were the extraocular muscles, the tibialis anterior, the oculormoter neuron, and the abducen motor neuron.研究目的：婴儿型眼球震颤综合征（Infantile nystagmus syndrome, INS）是一类以共轭性、不受控眼球摆动为特征的注视维持障碍，可导致显著视力下降。该疾病常与白化病相关，但其具体发病机制尚未明确。白化小鼠已被证实可出现眼球震颤表型，但此前针对携带酪氨酸酶（tyrosinase, TYR）突变、表型呈白化的色素型小鼠B6(CG)-Tyr(c-2J)/J（下称B6白化小鼠）的相关检测仍未开展。本研究对B6白化小鼠及对照小鼠开展了视动性眼球震颤反射（optokinetic nystagmus reflex, OKN）检测，并对眼外肌（extraocular muscles, EOM）、胫骨前肌（tibialis anterior muscle, TA）、展神经核（abducens, CN6）及动眼神经核（oculomotor, CN3）神经元进行RNA测序（RNA-Seq），以挖掘可解释眼球震颤发生的分子差异。本研究使用两种基因型的实验小鼠：B6(CG)-Tyr(c-2J)/J与C57BL/6，其中B6(CG)-Tyr(c-2J)/J为白化小鼠，C57BL/6为色素型小鼠。每种基因型均设置4次生物学重复，采集的组织类型包括眼外肌、胫骨前肌、动眼神经核神经元及展神经核运动神经元。