研究原钙粘蛋白γ - c4的新靶向转基因小鼠系

IF 2.4 4区 生物学 Q2 DEVELOPMENTAL BIOLOGY
genesis Pub Date : 2025-02-09 DOI:10.1002/dvg.70010
Cathy M. McLeod, Camille M. Hanes, Leah C. Fuller, Samjhana Bhandari, Hannah G. Lanthier, Robert W. Burgess, Joshua A. Weiner, Andrew M. Garrett
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引用次数: 0

摘要

γ-原钙粘蛋白(γ-Pcdhs)由22种亲同型细胞粘附分子组成,由Pcdhg基因簇通过启动子选择机制表达,在神经发育过程中起着许多重要作用。新出现的证据支持不同同种异构体具有独特功能的假设。γ- c4异构体由Pcdhgc4启动子表达,包括其独特的可变外显子,是小鼠出生后生存所必需的唯一γ-Pcdh异构体。在这里,我们描述了一个新的小鼠系(C4-GFP),在Cre重组酶切除lox-Stop-lox盒后,带有c端GFP标签的Pcdhgc4从Rosa26位点表达。我们报道,使用nesting - cre在神经系统中限制性表达该转基因足以挽救Pcdhgc4突变体小鼠的新生儿死亡。这一新产品线将成为解剖这种基本细胞粘附分子基因的功能机制的重要工具,这种基因的突变与人类神经发育障碍有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A New Targeted Transgenic Mouse Line for the Study of Protocadherin γC4

The γ-protocadherins (γ-Pcdhs) comprise 22 homophilic cell adhesion molecule isoforms, expressed from the Pcdhg gene cluster via promoter choice mechanisms that serve many crucial functions during neural development. Emerging evidence supports the hypothesis that distinct isoforms have unique functions. The γC4 isoform, which is expressed from the Pcdhgc4 promoter and includes its unique variable exon, is the sole γ-Pcdh isoform essential for the postnatal survival in mice. Here we describe a new mouse line (C4-GFP) in which Pcdhgc4 with a C-terminal GFP tag is expressed from the Rosa26 locus following excision of a lox-Stop-lox cassette by Cre recombinase. We report that restricted expression of this transgene in the nervous system using Nestin-Cre is sufficient to rescue the neonatal lethality of mice mutant for Pcdhgc4. This new line will be a vital tool for dissecting mechanisms underlying the functions of this essential cell adhesion molecule gene, mutations in which have been associated with neurodevelopmental disorders in humans.

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来源期刊
genesis
genesis 生物-发育生物学
CiteScore
3.60
自引率
0.00%
发文量
40
审稿时长
6-12 weeks
期刊介绍: As of January 2000, Developmental Genetics was renamed and relaunched as genesis: The Journal of Genetics and Development, with a new scope and Editorial Board. The journal focuses on work that addresses the genetics of development and the fundamental mechanisms of embryological processes in animals and plants. With increased awareness of the interplay between genetics and evolutionary change, particularly during developmental processes, we encourage submission of manuscripts from all ecological niches. The expanded numbers of genomes for which sequencing is being completed will facilitate genetic and genomic examination of developmental issues, even if the model system does not fit the “classical genetic” mold. Therefore, we encourage submission of manuscripts from all species. Other areas of particular interest include: 1) the roles of epigenetics, microRNAs and environment on developmental processes; 2) genome-wide studies; 3) novel imaging techniques for the study of gene expression and cellular function; 4) comparative genetics and genomics and 5) animal models of human genetic and developmental disorders. genesis presents reviews, full research articles, short research letters, and state-of-the-art technology reports that promote an understanding of the function of genes and the roles they play in complex developmental processes.
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