Kmt5b-KO 基因敲除小鼠

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产品名称

Kmt5b-KO 基因敲除小鼠

产品编号

S-KO-17434

品系全称

C57BL/6JCya-Kmt5bem1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-225888-Kmt5b-B6J-VA

品系状态

使用本品系发表的文献需注明: Kmt5b-KO 基因敲除小鼠 mice (Strain S-KO-17434) 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
lysine methyltransferase 5B
基因别称
C630029K18Rik,Suv4-20h1,Suv420h1
染色体号
Chr 19 (Mouse)
转录本 ID
NCBI: NM_001167885 | Ensembl: ENSMUST00000113973
修饰方式
全身性基因敲除
靶向范围
Exon 5
敲除长度
~1.2 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:2444557Mice homozygous for a knock-out allele are born at sub-Mendelian ratios, are smaller than control littermates, and die within a few hours of birth, probably due to alveolar defects.
KMT5B,也称为SUV420H1,是一种重要的组蛋白H4K20二甲基和三甲基转移酶,在人类前额叶皮质中高表达。KMT5B在神经发育过程中发挥着关键作用,其功能缺陷与多种神经发育障碍(NDDs)相关,包括自闭症谱系障碍(ASD)和智力障碍(ID)。KMT5B的突变导致组蛋白修饰异常,进而影响基因转录、DNA修复和神经元发育,导致神经功能障碍。

研究发现,KMT5B基因突变与自闭症谱系障碍(ASD)的发生密切相关。在ASD患者中,KMT5B基因突变导致神经元发育异常,包括神经元突触功能障碍、神经元迁移障碍和神经环路活动异常。这些神经元发育异常导致患者出现社交障碍、语言障碍和重复刻板行为等症状[1][2][3]。

KMT5B基因突变还与智力障碍(ID)相关。KMT5B基因突变导致组蛋白修饰异常,进而影响基因转录和DNA修复,导致智力发育迟缓。研究发现,KMT5B基因突变的患者表现出智力障碍、语言障碍、面部畸形和巨颅症等症状[4][5]。

此外,KMT5B基因突变还与发育迟缓相关。研究发现,KMT5B基因突变的患者表现出生长发育迟缓、肌肉发育不良和运动障碍等症状[6][7]。

KMT5B基因突变还与染色体调节相关。研究发现,KMT5B基因突变导致染色体结构异常,进而影响基因转录和DNA修复,导致神经发育障碍[8][9]。

综上所述,KMT5B基因在神经发育过程中发挥着重要作用,其功能缺陷与多种神经发育障碍(NDDs)相关。KMT5B基因突变导致组蛋白修饰异常,进而影响基因转录、DNA修复和神经元发育,导致神经功能障碍。未来,KMT5B基因的研究将为神经发育障碍的发病机制和治疗提供新的思路和策略。

参考文献:
1. Stessman, Holly A F, Xiong, Bo, Coe, Bradley P, Bernier, Raphael A, Eichler, Evan E. 2017. Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. In Nature genetics, 49, 515-526. doi:10.1038/ng.3792. https://pubmed.ncbi.nlm.nih.gov/28191889/
2. Paulsen, Bruna, Velasco, Silvia, Kedaigle, Amanda J, Levin, Joshua Z, Arlotta, Paola. 2022. Autism genes converge on asynchronous development of shared neuron classes. In Nature, 602, 268-273. doi:10.1038/s41586-021-04358-6. https://pubmed.ncbi.nlm.nih.gov/35110736/
3. Wang, Zi-Jun, Rein, Ben, Zhong, Ping, Ma, Kaijie, Yan, Zhen. 2021. Autism risk gene KMT5B deficiency in prefrontal cortex induces synaptic dysfunction and social deficits via alterations of DNA repair and gene transcription. In Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 46, 1617-1626. doi:10.1038/s41386-021-01029-y. https://pubmed.ncbi.nlm.nih.gov/34007043/
4. Faundes, Víctor, Newman, William G, Bernardini, Laura, Temple, I Karen, Banka, Siddharth. 2017. Histone Lysine Methylases and Demethylases in the Landscape of Human Developmental Disorders. In American journal of human genetics, 102, 175-187. doi:10.1016/j.ajhg.2017.11.013. https://pubmed.ncbi.nlm.nih.gov/29276005/
5. Eliyahu, Aviva, Barel, Ortal, Greenbaum, Lior, Shohat, Mordechai, Pode-Shakked, Ben. 2022. Refining the Phenotypic Spectrum of KMT5B-Associated Developmental Delay. In Frontiers in pediatrics, 10, 844845. doi:10.3389/fped.2022.844845. https://pubmed.ncbi.nlm.nih.gov/35433545/
6. Wickramasekara, Rochelle N, Robertson, Brynn, Hulen, Jason, Hallgren, Jodi, Stessman, Holly A F. 2021. Differential effects by sex with Kmt5b loss. In Autism research : official journal of the International Society for Autism Research, 14, 1554-1571. doi:10.1002/aur.2516. https://pubmed.ncbi.nlm.nih.gov/33871180/
7. Chen, Guodong, Han, Lin, Tan, Senwei, Xia, Kun, Guo, Hui. 2022. Loss-of-function of KMT5B leads to neurodevelopmental disorder and impairs neuronal development and neurogenesis. In Journal of genetics and genomics = Yi chuan xue bao, 49, 881-890. doi:10.1016/j.jgg.2022.03.004. https://pubmed.ncbi.nlm.nih.gov/35331928/
8. Hulen, Jason, Kenny, Dorothy, Black, Rebecca, Abel, Peter W, Stessman, Holly A F. 2022. KMT5B is required for early motor development. In Frontiers in genetics, 13, 901228. doi:10.3389/fgene.2022.901228. https://pubmed.ncbi.nlm.nih.gov/36035149/
9. Lasser, Micaela, Sun, Nawei, Xu, Yuxiao, Willsey, A Jeremy, Willsey, Helen Rankin. 2023. Pleiotropy of autism-associated chromatin regulators. In Development (Cambridge, England), 150, . doi:10.1242/dev.201515. https://pubmed.ncbi.nlm.nih.gov/37366052/