Commonly Used Myh11-CreERT2Strain Carries a Y-Linked Functional Wild-Type Tlr7 Allele.

Commonly Used Myh11-CreERT2Strain Carries a Y-Linked Functional Wild-Type Tlr7 Allele.
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常用的 Myh11-CreERT2 菌株携带 Y 连锁功能野生型 Tlr7 等位基因。

DOI:
10.1161/atvbaha.122.318919
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发表时间:
2023
期刊:
Arteriosclerosis, thrombosis, and vascular biology
影响因子:
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通讯作者:
Jiang,Zhihua
Jiang,Zhihua
中科院分区:
--
文献类型:
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作者:
Li,Jie;Xu,Haiyan;Hung,Alex;Javed,MuhammadJavad;UpchurchJr,GilbertR;Jiang,Zhihua

文献摘要

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Wirth et AL1创造的MYH11-Creer小鼠由于其相对较高的谱系特异性,是最适合用于平滑肌细胞特异性基因缺失或激活的Cre系。然而,该菌株的基因组似乎不稳定。我们报道了MYH11-Creer等位基因可以从Y-染色体易位到X-染色体。2本研究描述了另一个令人惊讶但又至关重要的发现,MYH11-Creer小鼠在X染色体和Y染色体上分别携带两个活跃的TLR7等位基因。TLR7位于X染色体上。因此,我们预计Tgfbr1f/f.MYH11-Creer+雄性和Tgfbr1f/f.TLR7-−/−雌性育种者产生的雄性后代都是TLR7零,都是Tgfbr1f/f.TLR7-/y.MYH11-Creer+基因型。令人惊讶的是,基因分型结果显示,他们(n=43)各自获得了父源(野生型[WT])和母源突变的TLR7等位基因,最终得到了Tgfbr1f/f.TLR7−/w.MYH11-Creer+的基因型。WTTLR7DNA序列与天然TLR7DNA序列相同(图[A])。由于位于父本X染色体上的基因不会遗传给男性后代,我们推测WT TLR7等位基因位于常染色体或Y染色体上。
The Myh11-CreER mouse created by Wirth et al1 was the most preferred Cre line for smooth muscle cell–specific gene deletion or activation due to its relatively high lineage specificity. However, the genome of this strain appear to be unstable. We reported that the Myh11-CreER allele can translocate from the Y-to the X-chromosome. 2 The present study describes another surprising, yet critical, finding that the Myh11-CreER mouse carries 2 copies of active Tlr7 alleles on the X-and the Y-chromosome, respectively. Tlr7 is located on the X-chromosome. Accordingly, we expected that male progeny produced by Tgfbr1f/f. Myh11-CreER+ male and Tgfbr1f/f. Tlr7−/− female breeders would all be Tlr7 null and on a Tgfbr1f/f. Tlr7-/y. Myh11-CreER+ genotype. Surprisingly, genotyping results showed that they (n= 43) each obtained a paternal origin (wild type [WT]) and a maternal origin mutated Tlr7 alleles, culminating on a genotype of Tgfbr1f/f. Tlr7−/w. Myh11-CreER+.The DNA sequence of the WT Tlr7 is identical to that of the natural Tlr7 (Figure [A]). Since genes located on the paternal X-chromosome are not be passed to male offspring, we suspected that the WT Tlr7 allele is located either on an autosome or the Y-chromosome.