Heart development in fibronectin-null mice is governed by a genetic modifier on chromosome four
Heart development in fibronectin-null mice is governed by a genetic modifier on chromosome four
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DOI：
10.1016/j.mod.2007.05.004
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发表时间：
2007-08-01
影响因子：
2.6
通讯作者：
Hynes, Richard O.
中科院分区：
文献类型：
--
作者：
Astrof, Sophie;Kirb, Andrew;Hynes, Richard O.
由于严重的心血管缺陷，在129S4和C57BL/6J菌株中，纤维连接蛋白(FN)基因的缺失都会导致早期胚胎死亡。然而，根据遗传背景的不同，心脏发育在这些胚胎中处于不同的阶段。在大多数129S4 Fn缺失胚胎中，心脏祖细胞保持在它们的双侧前位置，而不能在中线融合形成心管。然而，在C57BL/6J的遗传背景下，心脏发育进一步发展，并导致中心定位和环状心脏。为了在129S4和C57BL/6J品系的Fn缺失胚胎中寻找参与胚胎心脏形成和控制心脏发育程度的因子(S)，我们进行了遗传作图和单倍型分析。这些分析导致了与四号染色体上1-MBP区间的显著连锁。微阵列分析和测序确定了该区域的21个基因，其中包括5个在菌株之间差异表达的基因，作为潜在的修饰基因。由于这些基因之前都不知道在心脏发育中起作用，它们中的一个或多个很可能是影响心脏发育的新修饰物。修饰物的鉴定将大大增强我们对心脏发育和疾病的分子基础的理解。(C)2007爱思唯尔爱尔兰有限公司。保留所有权利。
Absence of the fibronectin (FN) gene leads to early embryonic lethality in both 129S4 and C57BL/6J strains due to severe cardiovascular defects. However, heart development is arrested at different stages in these embryos depending on the genetic background. In the majority of 129S4 FN-null embryos, heart progenitors remain at their anterior bilateral positions and fail to fuse at the midline to form a heart tube. However, on the C57BL/6J genetic background, cardiac development progresses further and results in a centrally positioned and looped heart. To find factor(s) involved in embryonic heart formation and governing the extent of heart development in FN-null embryos in 129S4 and C57BL/6J strains, we performed genetic mapping and haplotype analyses. These analyses lead to identification of a significant linkage to a 1-Mbp interval on chromosome four. Microarray analysis and sequencing identified 21 genes in this region, including five that are differentially expressed between the strains, as potential modifiers. Since none of these genes was previously known to play a role in heart development, one or more of them is likely to be a novel modifier affecting cardiac development. Identification of the modifier would significantly enhance our understanding of the molecular underpinning of heart development and disease. (c) 2007 Elsevier Ireland Ltd. All rights reserved.