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一种p57条件突变等位基因,可用于追踪表达p57的细胞。

A p57 conditional mutant allele that allows tracking of p57-expressing cells.

作者信息

Mademtzoglou Despoina, Alonso-Martin Sonia, Chang Ted Hung-Tse, Bismuth Keren, Drayton-Libotte Bernadette, Aurade Frédéric, Relaix Frédéric

机构信息

Inserm, IMRB U955-E10, Creteil, F-94010, France.

Université Paris Est, Faculté de medecine, F-94000, Creteil, & Ecole Nationale Veterinaire d'Alfort, Maison Alfort, 94700, France.

出版信息

Genesis. 2017 Apr;55(4). doi: 10.1002/dvg.23025. Epub 2017 Apr 4.

Abstract

p57 (p57) is a maternally expressed imprinted gene regulating growth arrest which belongs to the CIP/KIP family of cyclin-dependent kinase inhibitors. While initially identified as a cell cycle arrest protein through inhibition of cyclin and cyclin-dependent kinase complexes, p57 activity has also been linked to differentiation, apoptosis, and senescence. In addition, p57 has recently been shown to be involved in tumorigenesis and cell fate decisions in stem cells. Yet, p57 function in adult tissues remains poorly characterized due to the perinatal lethality of p57 knock-out mice. To analyze p57 tissue-specific activity, we generated a conditional mouse line (p57 ) by flanking the coding exons 2-3 by LoxP sites. To track p57-expressing or mutant cells, the p57 allele also contains an IRES-linked β-galactosidase reporter inserted in the 3' UTR of the gene. Here, we show that the β-galactosidase reporter expression pattern recapitulates p57 tissue specificity during development and in postnatal mice. Furthermore, we crossed the p57 mice with PGK-Cre mice to generate p57 animals with ubiquitous loss of p57. p57 mice display developmental phenotypes analogous to previously described p57 knock-outs. Thus, p57 is a new genetic tool allowing expression and functional conditional analyses of p57.

摘要

p57(p57)是一种由母体表达的印记基因,可调节生长停滞,属于细胞周期蛋白依赖性激酶抑制剂的CIP/KIP家族。虽然最初是通过抑制细胞周期蛋白和细胞周期蛋白依赖性激酶复合物而被鉴定为细胞周期停滞蛋白,但p57的活性也与分化、凋亡和衰老有关。此外,最近已表明p57参与肿瘤发生和干细胞中的细胞命运决定。然而,由于p57基因敲除小鼠的围产期致死性,p57在成体组织中的功能仍知之甚少。为了分析p57的组织特异性活性,我们通过在编码外显子2-3两侧侧翼插入LoxP位点,构建了一个条件性小鼠品系(p57)。为了追踪表达p57或突变的细胞,p57等位基因还包含一个插入到该基因3'UTR中的与IRES相连的β-半乳糖苷酶报告基因。在此,我们表明β-半乳糖苷酶报告基因的表达模式在发育过程中和出生后的小鼠中概括了p57的组织特异性。此外,我们将p57小鼠与PGK-Cre小鼠杂交,以产生普遍缺失p57的p57动物。p57小鼠表现出与先前描述的p57基因敲除类似的发育表型。因此,p57是一种新的遗传工具,可用于对p57进行表达和功能条件分析。

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