Minimal Aberrant Behavioral Phenotypes of Neuroligin-3 R451C Knockin Mice
Minimal Aberrant Behavioral Phenotypes of Neuroligin-3 R451C Knockin Mice
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DOI：
10.1002/aur.22
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发表时间：
2008-06-01
期刊：
影响因子：
4.7
通讯作者：
Crawley, Jacqueline N.
中科院分区：
文献类型：
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作者：
Chadman, Kathryn K.;Gong, Shiaoching;Crawley, Jacqueline N.
Neuroligin-3 是介导突触发育并与自闭症有关的细胞粘附蛋白类别的成员。具有人类 R451C 突变 (NL3) 的小鼠与患有自闭症谱系障碍的两兄弟中发现的点突变相同，在多种行为测定中产生并进行表型分析，这些小鼠对自闭症的诊断症状具有表面有效性。在青少年相互社交互动、成年社交方式、认知能力和对空间习惯改变的抵抗力方面，NL3 与其野生型 (WT) 同窝对照之间没有检测到差异，这一发现在几个雄性和雌性队列中得到了重复。在一般健康、感觉能力、感觉运动门控、运动功能和焦虑相关特征的测量方面，不同基因型的身体和程序能力相似。 NL3 和 WT 之间检测到微小的发育差异，包括体细胞生长速度略有不同、出生后第 2-6 天翻正反射较慢、雌性归巢反射较快、雄性出生后第 8 天发声较少。 NI,3 成虫的显着差异包括从转棒上坠落的潜伏期较长、开阔场地中的垂直活动较少以及对高分贝音调的声音惊吓较少。小鼠中的人源化 R451C 突变并未导致明显的自闭症样表型，但产生了可检测到的功能后果，这些后果可以用身体发育和/或对刺激的敏感性降低来解释。
Neuroligin-3 is a member of the class of cell adhesion proteins that mediate synapse development and have been implicated in autism. Mice with the human R451C mutation (NL3), identical to the point mutation found in two brothers with autism spectrum disorders, were generated and phenotyped in multiple behavioral assays with face validity to the diagnostic symptoms of autism. No differences between NL3 and their wildtype (WT) littermate controls were detected on measures of juvenile reciprocal social interaction, adult social approach, cognitive abilities, and resistance to change in a spatial habit, findings which were replicated in several cohorts of males and females. physical and procedural abilities were similar across genotypes on measures of general health, sensory abilities, sensorimotor gating, motor functions, and anxiety-related traits. Minor developmental differences were detected between NL3 and WT, including slightly different rates of somatic growth, slower righting reflexes at postnatal days 2-6, faster homing reflexes in females, and less vocalizations on postnatal day 8 in males. Significant differences in NI,3 adults included somewhat longer latencies to fall from the rotarod, less vertical activity in the open field, and less acoustic startle to high decibel tones. The humanized R451C mutation in mice did not result in apparent autism-like phenotypes, but produced detectable functional consequences that may be interpreted in terms of physical development and/or reduced sensitivity to stimuli.