Nagpa-KO 基因敲除小鼠

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产品名称

Nagpa-KO 基因敲除小鼠

产品编号

S-KO-16357

品系全称

C57BL/6JCya-Nagpaem1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-27426-Nagpa-B6J-VB

品系状态

使用本品系发表的文献需注明: Nagpa-KO 基因敲除小鼠 mice (Strain S-KO-16357) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量

基本信息

基因研究概述

质控标准

基因
基因全称
N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase
基因别称
UCE
染色体号
Chr 16 (Mouse)
转录本 ID
NCBI: NM_013796.3 | Ensembl: ENSMUST00000023911
修饰方式
全身性基因敲除
靶向范围
Exon 3
敲除长度
~0.9 kb
品系说明
该品系是基于策略设计时的数据库信息制作而成,建议您在购买前查询最新的数据库和相关文献,以获取最准确的表型信息。
表型提示
MGI:1351598Mice homozygous for a null allele have an increased level of acid hydrolases, however the hydrolases contain GlcNAc-P-Man diesters, exhibit a decreased affinity for the cation-independent mannose 6-phosphate receptor and fail to bind to the cation-dependent mannose 6-phosphate receptor.
NAGPA,也称为N-乙酰氨基葡萄糖-1-磷酸二酯α-N-乙酰氨基葡萄糖苷酶,是一种重要的溶酶体酶靶向通路基因。溶酶体是一种细胞内的膜结合结构,负责分解和回收细胞内的废物和受损的细胞器。溶酶体需要多种水解酶来分解这些大分子物质,而这些水解酶需要通过特定的途径被靶向到溶酶体内。NAGPA编码的蛋白质参与这一途径,它是一种Golgi定位的跨膜蛋白,负责维持GlcNAc-1-磷酸转移酶复合物在Golgi器内的稳定。GlcNAc-1-磷酸转移酶复合物是溶酶体酶靶向通路的关键组成部分,它将N-乙酰氨基葡萄糖-1-磷酸(M6P)基团添加到水解酶上,使得这些水解酶能够被识别并被运输到溶酶体内。

NAGPA基因的突变与多种疾病有关。例如,GNPTAB和GNPTG基因的突变会导致粘多糖症II型和III型,这是两种罕见的常染色体隐性溶酶体贮积症,与骨骼、结缔组织、肝脏、脾脏和大脑的病理学有关。尽管NAGPA基因的突变尚未与人类疾病相关联,但研究表明,NAGPA基因的突变与持续性发育性口吃有关。口吃是一种常见的言语障碍,其特征是言语流利性的中断,包括重复、延长和不由自主的停顿。研究发现,NAGPA基因的突变会降低编码的酶的活性,导致细胞内加工和转运的缺陷,进而影响口吃的神经病理学。

NAGPA基因的研究不仅限于口吃。研究还发现,NAGPA基因的变异与阅读障碍有关。阅读障碍是一种多基因的言语和语言障碍,其特征是儿童和成人尽管智力正常,但在阅读方面存在困难。研究发现,NAGPA基因的变异与阅读障碍的发生有关。此外,NAGPA基因的变异还与川崎病和免疫球蛋白A血管炎有关。川崎病是一种儿童时期的血管炎性疾病,而免疫球蛋白A血管炎是一种儿童时期的炎症性疾病。研究发现,NAGPA基因中的遗传变异与川崎病和免疫球蛋白A血管炎的发生有关。

总之,NAGPA基因在溶酶体酶靶向通路中发挥着重要作用,其突变与多种疾病有关,包括口吃、阅读障碍、川崎病和免疫球蛋白A血管炎。NAGPA基因的研究有助于深入理解溶酶体酶靶向通路的功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略[1,2,3,4,5,6,7,8,9,10]。

参考文献:
1. Gunasekaran, Nandhini Devi, Jayasankaran, Chandru, Justin Margret, Jeffrey, Krishnamoorthy, Mathuravalli, Srisailapathy, C R Srikumari. 2021. Evaluation of recurrent GNPTAB, GNPTG, and NAGPA variants associated with stuttering. In Advanced genetics (Hoboken, N.J.), 2, e10043. doi:10.1002/ggn2.10043. https://pubmed.ncbi.nlm.nih.gov/36618124/
2. Kang, Changsoo, Drayna, Dennis. . Genetics of speech and language disorders. In Annual review of genomics and human genetics, 12, 145-64. doi:10.1146/annurev-genom-090810-183119. https://pubmed.ncbi.nlm.nih.gov/21663442/
3. Han, Tae-Un, Park, John, Domingues, Carlos F, Gutierrez, Joanne, Drayna, Dennis. 2014. A study of the role of the FOXP2 and CNTNAP2 genes in persistent developmental stuttering. In Neurobiology of disease, 69, 23-31. doi:10.1016/j.nbd.2014.04.019. https://pubmed.ncbi.nlm.nih.gov/24807205/
4. Kang, Changsoo, Drayna, Dennis. 2012. A role for inherited metabolic deficits in persistent developmental stuttering. In Molecular genetics and metabolism, 107, 276-80. doi:10.1016/j.ymgme.2012.07.020. https://pubmed.ncbi.nlm.nih.gov/22884963/
5. Chen, Huan, Xu, Junquan, Zhou, Yuxi, Tan, Li Hai, Sun, Yimin. 2015. Association study of stuttering candidate genes GNPTAB, GNPTG and NAGPA with dyslexia in Chinese population. In BMC genetics, 16, 7. doi:10.1186/s12863-015-0172-5. https://pubmed.ncbi.nlm.nih.gov/25643770/
6. Qiao, Wenjie, Richards, Christopher M, Jabs, Sabrina. 2023. LYSET/TMEM251- a novel key component of the mannose 6-phosphate pathway. In Autophagy, 19, 2143-2145. doi:10.1080/15548627.2023.2167376. https://pubmed.ncbi.nlm.nih.gov/36633450/
7. Frigerio-Domingues, Carlos E, Gkalitsiou, Zoi, Zezinka, Alexandra, Webster, Ronald, Drayna, Dennis. 2019. Genetic factors and therapy outcomes in persistent developmental stuttering. In Journal of communication disorders, 80, 11-17. doi:10.1016/j.jcomdis.2019.03.007. https://pubmed.ncbi.nlm.nih.gov/31003007/
8. Nandhini Devi, G, Yadav, Navneesh, Jayashankaran, Chandru, Thelma, B K, Srisailapathy, C R Srikumari. 2024. Genetic analyses of a large consanguineous south Indian family reveal novel variants in NAGPA and four hitherto unreported genes in developmental stuttering. In Annals of human genetics, 89, 31-46. doi:10.1111/ahg.12579. https://pubmed.ncbi.nlm.nih.gov/39382170/
9. Kazemi, Nima, Estiar, Mehrdad Asghari, Fazilaty, Hassan, Sakhinia, Ebrahim. 2017. Variants in GNPTAB, GNPTG and NAGPA genes are associated with stutterers. In Gene, 647, 93-100. doi:10.1016/j.gene.2017.12.054. https://pubmed.ncbi.nlm.nih.gov/29289611/
10. Carmona, Elio G, García-Giménez, Jose A, López-Mejías, Raquel, Martín, Javier, Márquez, Ana. . Identification of a shared genetic risk locus for Kawasaki disease and immunoglobulin A vasculitis by a cross-phenotype meta-analysis. In Rheumatology (Oxford, England), 61, 1204-1210. doi:10.1093/rheumatology/keab443. https://pubmed.ncbi.nlm.nih.gov/33993232/