Heterotaxy-spectrum heart defects in Zic3 hypomorphic mice.
Heterotaxy-spectrum heart defects in Zic3 hypomorphic mice.
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DOI：
10.1038/pr.2013.147
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发表时间：
2013-11
影响因子：
3.6
通讯作者：
Ware, Stephanie M.
中科院分区：
文献类型：
--
作者：
Haaning, Allison M.;Quinn, Malgorzata E.;Ware, Stephanie M.
ZIC3突变导致X连锁异位和孤立的心血管畸形。最近的数据表明，Zic 3通过调节Nppa和Tbx5在心肌中具有潜在的细胞自主作用。我们试图开发一种亚纯型Zic 3小鼠来模拟人类内脏异位，并研究心脏表型变异的发育机制。通过靶向插入新霉素盒产生Zic 3亚纯型小鼠，并通过大体、组织学和分子方法研究，与Zic 3缺失小鼠相比，低水平Zic 3表达足以部分挽救生存力。早期左右分子标记异常和后来的解剖学异常的一致性表明，Zic 3在心脏发育中的主要作用发生在左右模式期间。Nppa（ANF）和Tbx5的心脏特异性基因表达标记了心脏中的适当形态学位置，而不管循环异常。Zic3亚纯型小鼠是研究单一遗传缺陷导致的可变心脏缺陷的有用模型。低水平Zic 3表达挽救了Zic 3缺失胚胎中鉴定的左肺异构。我们的数据不支持Zic 3通过调节Nppa和Tbx5在心肌中的直接作用，并表明Zic 3对心脏发育的主要作用发生在左右模式期间。
Mutations in ZIC3 cause X-linked heterotaxy and isolated cardiovascular malformations. Recent data suggest a potential cell-autonomous role for Zic3 in myocardium via regulation of Nppa and Tbx5. We sought to develop a hypomorphic Zic3 mouse to model human heterotaxy and investigate developmental mechanisms underlying variability in cardiac phenotypes. Zic3 hypomorphic mice were created by targeted insertion of a neomycin cassette and investigated by gross, histologic, and molecular methods Low level Zic3 expression is sufficient for partial rescue of viability as compared to Zic3 null mice. Concordance of early left-right molecular marker abnormalities and later anatomic abnormalities suggests the primary effect of Zic3 in heart development occurs during left-right patterning. Cardiac specific gene expression of Nppa (ANF) and Tbx5 marked the proper morphological locations in the heart regardless of looping abnormalities. Zic3 hypomorphic mice are a useful model to investigate the variable cardiac defects resulting from a single genetic defect. Low level Zic3 expression rescues the left pulmonary isomerism identified in Zic3 null embryos. Our data do not support a direct role for Zic3 in the myocardium via regulation of Nppa and Tbx5 and suggest the primary effect of Zic3 on cardiac development occurs during left-right patterning.
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影响因子：
5.2
作者：
Mégarbané, A;Salem, N;Bouvagnet, A
通讯作者：
Bouvagnet, A
DOI：
10.1073/pnas.96.20.11376
发表时间：
1999-09-28
影响因子：
11.1
作者：
Tsukui, T;Capdevila, J;Belmonte, JCI
通讯作者：
Belmonte, JCI
影响因子：
37.8
作者：
Oyen, Nina;Poulsen, Gry;Melbye, Mads
通讯作者：
Melbye, Mads
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.6
作者：
Takeuchi, JK;Ohgi, M;Ogura, T
通讯作者：
Ogura, T