遗传性痉挛性截瘫相关受体表达增强蛋白2在小鼠脑内的表达

齐书畅 杨姝 鲁玲玲

解剖学报 ›› 2026, Vol. 57 ›› Issue (4) : 418-424.

PDF(1242 KB)
欢迎访问《解剖学报》官方网站!今天是 English
PDF(1242 KB)
解剖学报 ›› 2026, Vol. 57 ›› Issue (4) : 418-424. DOI: 10.16098/j.issn.0529-1356.2026.04.004
神经生物学

遗传性痉挛性截瘫相关受体表达增强蛋白2在小鼠脑内的表达

  • 齐书畅杨姝鲁玲玲3*
作者信息 +

Expression of receptor expression-enhancing protein 2 associated with hereditary spastic paraplegia in mouse brains

  • QI Shu-chang1, YANG Shu2, LU Ling-ling3*
Author information +
文章历史 +

摘要

目的 探讨成年小鼠全脑受体表达增强蛋白2 (REEP2) 的表达与分布,为解析REEP2在神经系统中的生理功能及其参与遗传性痉挛性截瘫(HSP)等疾病发生的分子机制提供形态学依据。方法 采用人类蛋白质数据库(HPA)分析与免疫组织化学技术相结合的策略,对6只成年小鼠脑组织切片进行REEP2蛋白免疫标记,利用数字扫描显微成像系统进行全脑切片图像采集,并依据标准小鼠脑图谱对阳性表达区域进行解剖结构及细胞类型的精确识别与定位。结果 REEP2蛋白在成年小鼠脑内广泛表达,包括大脑皮质、丘脑、小脑和海马结构。进行REEP2蛋白阳性部位、阳性细胞的定位和分析显示,其主要表达于神经元的胞体和树突内,REEP2阳性染色均呈现棕黄色颗粒,其中在大脑皮质锥体神经元、基底神经节尾壳核神经元、丘脑的腹后内侧核和腹后外侧核、丘脑外侧核群如丘脑外侧后核神经元及小脑浦肯野细胞中呈高表达,在海马结构神经元中呈中等强度表达。结论 REEP2在大脑皮质、小脑、纹状体、丘脑、海马等多个脑区高丰度表达,为后续构建条件性基因敲除动物模型,深入研究REEP2蛋白异常在HSP发病中的作用机制及相关脑内功能研究提供了重要的形态学依据。

Abstract

Objective To investigate the expression and localization of receptor expression-enhancing protein 2(REEP2) protein throughout the adult mouse brain, providing essential anatomical insights into its physiological functions and mechanistic involvement in hereditary spastic paraplegias (HSP). Methods An integrated approach combining Human Protein Atlas (HPA) database analysis and immunohistochemical techniques were employed. Brain sections from 6 adult mice were used for REEP2 immunohistochemical staining. Whole-brain section imaging was acquired using a digital scanning microscopic imaging system, with precise anatomical identification and localization of positively expressed regions based on the standard mouse brain atlas. Results REEP2 protein was widely expressed in the brains of adult mice, including the cerebral cortex, thalamus, cerebellum, and hippocampus. Localization and analysis of REEP2-positive regions and cells revealed its predominant expression in neuronal cell bodies and dendrites, with all REEP2-positive structures appearing as brownish-yellow granules. Notably, high expression was observed in pyramidal neurons of the cerebral cortex, caudate and putamen neurons of the basal ganglia, the ventral posterior medial and lateral nuclei of the thalamus, and the lateral nucleus group of the thalamus (e.g., the lateral posterior nucleus neurons) as well as cerebellar Purkinje cells. In hippocampal neurons, it showed moderate expression. Conclusion REEP2 protein is enriched in several brain regions, e.g. cortex, cerebellum, striatum, thalamus, hippocampus, etc. This study elucidates the spatial expression profile of REEP2 protein in the adult mouse brain. The findings provide crucial morphological evidence for subsequent development of conditional knockout animal models and further investigation into the role of REEP2 dysfunction in HSP pathogenesis, as well as its broader neural functions.

关键词

受体表达增强蛋白2 / 神经元 / 遗传性痉挛性截瘫 / 免疫组织化学 / 小鼠

Key words

Receptor expression-enhancing protein 2 / Neuron / Hereditary spastic paraplegia / Immunohistochemistry / Mouse

引用本文

导出引用
齐书畅 杨姝 鲁玲玲. 遗传性痉挛性截瘫相关受体表达增强蛋白2在小鼠脑内的表达[J]. 解剖学报. 2026, 57(4): 418-424 https://doi.org/10.16098/j.issn.0529-1356.2026.04.004
QI Shu-chang, YANG Shu, LU Ling-ling.
Expression of receptor expression-enhancing protein 2 associated with hereditary spastic paraplegia in mouse brains
[J]. Acta Anatomica Sinica. 2026, 57(4): 418-424 https://doi.org/10.16098/j.issn.0529-1356.2026.04.004
中图分类号: R32    R741.02   

参考文献

[1] Mainland J, Matsunami H. RAMP like proteins: RTP and REEP family of proteins [J]. Adv Exp Med Biol, 2012, 744: 75-86.
[2] Fan S, Liu H, Li L. The REEP family of proteins: molecular targets and role in pathophysiology [J]. Pharmacol Res, 2022, 185: 106477.
[3] Park SH, Zhu PP, Parker RL, et al. Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network [J]. J Clin Invest, 2010, 120(4): 1097-1110.
[4] Kumar D, Golchoubian B, Belevich I, et al. REEP3 and REEP4 determine the tubular morphology of the endoplasmic reticulum during mitosis [J]. Mol Biol Cell, 2019, 30(12): 1377-1389.
[5] Wang N, Clark LD, Gao Y, et al. Mechanism of membrane-curvature generation by ER-tubule shaping proteins [J]. Nat Commun, 2021, 12(1): 568.
[6] Esteves T, Durr A, Mundwiller E, et al. Loss of association of REEP2 with membranes leads to hereditary spastic paraplegia [J]. Am J Hum Genet, 2014, 94(2): 268-277.
[7] Nan H, Takaki R, Hata T, et al. A Nepalese family with an REEP2 mutation: clinical and genetic study [J]. J Hum Genet, 2021, 66(7): 749-752.
[8] Roda RH, Schindler AB, Blackstone C. De novo REEP2 missense mutation in pure hereditary spastic paraplegia [J]. Ann Clin Transl Neurol, 2017, 4(5): 347-350.
[9] Lo Giudice T, Lombardi F, Santorelli FM, et al. Hereditary spastic paraplegia: clinical-genetic characteristics and evolving molecular mechanisms [J]. Exp Neurol, 2014, 261: 518-539.
[10] De Beukelaer N, Bar-On L, Hanssen B, et al. Muscle characteristics in pediatric hereditary spastic paraplegia vs. bilateral spastic cerebral palsy: an exploratory study [J]. Front Neurol, 2021, 12: 635032.
[11] Zhi Y, Shi Y, Lu D, et al. Neurodevelopmental implications underpinning hereditary spastic paraplegia [J]. CNS Neurosci Ther, 2025, 31(2): e70260.
[12] Regensburger M, Spatz IT, Ollenschlager M, et al. Inertial gait sensors to measure mobility and functioning in hereditary spastic paraplegia: a cross-sectional multicenter clinical study [J]. Neurology, 2022, 99(10): e1079-e1089.
[13] Rodriguez-Moreno P, Loza-Vaqueiro J, Olivares-Moreno R, et al. Differential participation of the corticospinal and corticorubral neurons during motor execution in the rat [J]. Sci Rep, 2025, 15(1): 31998.
[14] Ilegems E, Iwatsuki K, Kokrashvili Z, et al. REEP2 enhances sweet receptor function by recruitment to lipid rafts [J]. J Neurosci, 2010, 30(41): 13774-13783.
[15] Sharoar MG, Shi Q, Ge Y, et al. Dysfunctional tubular endoplasmic reticulum constitutes a pathological feature of Alzheimer’s disease [J]. Mol Psychiatry, 2016, 21(9): 1263-1271.
[16] Heller E, Kurup N, Zhuang X. The membrane skeleton is constitutively remodeled in neurons by calcium signaling [J]. Science, 2025, 389(6760): adn6712.
[17] Liu XX, Chen XH, Zheng ZW, et al. BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination [J]. Signal Transduct Target Ther, 2022, 7(1): 170.
[18] Hurt CM, Bjork S, Ho VK, et al. REEP1 and REEP2 proteins are preferentially expressed in neuronal and neuronal-like exocytotic tissues [J]. Brain Res, 2014, 1545: 12-22.
[19] Xu L, Xiang Y, Hu J. Molecular basis of Climp63-mediated ER lumen spacing [J]. J Cell Sci, 2023, 136(9): jcs260976.


PDF(1242 KB)

Accesses

Citation

Detail

段落导航
相关文章

/