Department of Anatomy and Neurobiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8509, Japan.
Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8509, Japan.
Biochem Biophys Res Commun. 2021 Jul 23;563:66-72. doi: 10.1016/j.bbrc.2021.05.063. Epub 2021 May 29.
Kin of irregular chiasm-like 3 (Kirrel3), a member of the immunoglobulin superfamily, is expressed in the central nervous system during development and in adulthood. It has been reported that Kirrel3 is involved in the axonal fasciculation in the olfactory bulb, the neuronal migration in the pontine nucleus, and the synapse formation in the hippocampal neurons in mice. Although KIRREL3 mutations have been implicated in autism spectrum disorder and intellectual disability in humans, the comprehensive expression pattern of Kirrel3 in the adult brain is not fully understood. To better visualize Kirrel3 expression pattern and to gain insight into the role of Kirrel3 in the brain, we investigated the expression of Kirrel3 in the adult brain of Kirrel3-heterozygous (Kirrel3) mice, in which Kirrel3-expressing cells could be identified by the expression of β-galactosidase (β-gal) in the nucleus of cells. The strong expression of β-gal was observed in the hippocampus, cerebral cortex, olfactory bulb, amygdala, thalamus, and cerebellum. In the hippocampus, β-gal was detected in the dentate gyrus and in the ventral parts of CA1 and CA3, which are known to be involved in the social recognition memory. Within the cerebral cortex, many cells with β-gal expression were observed in the olfactory area and auditory area. In the striatum, neurons with β-gal expression were mainly observed in the ventral striatum. Expression of β-gal was observed in all layers in the cerebellum and olfactory bulb, except for the olfactory nerve layer. Double-immunofluorescence staining of β-galactosidase with neuronal markers revealed that β-gal expression was exclusively detected in neurons. These results suggest that Kirrel3 may be involved in the maintenance of neuronal networks, such as the maintenance of synaptic connectivity and plasticity in the motor, sensory, and cognitive circuits of adult brain.
免疫球蛋白超家族成员不规则交叉样 3（Kirrel3）的近亲在发育过程中和成年期中枢神经系统中表达。据报道，Kirrel3 参与了嗅球的轴突聚集、脑桥核中的神经元迁移以及海马神经元中的突触形成。尽管 KIRREL3 突变与人类自闭症谱系障碍和智力残疾有关，但 Kirrel3 在成年大脑中的全面表达模式尚未完全了解。为了更好地可视化 Kirrel3 的表达模式，并深入了解 Kirrel3 在大脑中的作用，我们研究了 Kirrel3 杂合子（Kirrel3）小鼠成年大脑中的 Kirrel3 表达。在这些小鼠中，细胞核中 β-半乳糖苷酶（β-gal）的表达可以识别出表达 Kirrel3 的细胞。在海马体、大脑皮层、嗅球、杏仁核、丘脑和小脑中观察到强烈的 β-gal 表达。在海马体中，β-gal 在齿状回和 CA1 和 CA3 的腹侧部分被检测到，已知这些部位参与社会识别记忆。在大脑皮层中，在嗅觉区和听觉区观察到许多带有 β-gal 表达的细胞。在纹状体中，主要在腹侧纹状体中观察到带有 β-gal 表达的神经元。在小脑和嗅球中，除嗅神经层外，所有层都观察到 β-gal 的表达。β-半乳糖苷酶与神经元标志物的双重免疫荧光染色显示，β-gal 表达仅在神经元中检测到。这些结果表明，Kirrel3 可能参与维持神经元网络，例如维持成年大脑运动、感觉和认知回路中的突触连接和可塑性。
