The Wheels mutation in the mouse causes vascular, hindbrain, and inner ear defects
The Wheels mutation in the mouse causes vascular, hindbrain, and inner ear defects
复制标题
DOI：
10.1006/dbio.2001.0241
复制
发表时间：
2001-06-01
影响因子：
2.7
通讯作者：
Bucan, M
中科院分区：
文献类型：
--
作者：
Alavizadeh, A;Kiernan, AE;Bucan, M
在筛选具有显性行为异常的小鼠突变时，我们确定了Wheels，这是一种与杂合子中的盘旋和过度活跃以及纯合子中的胚胎致死性相关的突变。突变的车轮胚胎在E10.5-E11.5死亡，并表现出许多形态异常，包括生长迟缓和血管和后脑发育异常。后者包括由Krox 20和Hoxb 1检测到的菱形边界的扰动。胚胎PECAM-1染色显示初级血管丛正常形成。然而，随后的分支和重塑阶段在卵黄囊和胚胎中不正常进行。为了深入了解盘旋的行为，我们检查了内耳的油漆填充的膜性耳蜗的Wh 1/+胚胎的发展。该分析显示E12.5时后半规管和外半规管原基较小，且半规管融合过程延迟。到E13.5，侧管被截断，后管变小或完全缺失。标记物分析揭示了一个早期的分子表型在杂合子胚胎的特点是扰动表达的Bmp 4和Msx 1在未来的侧和后嵴在E11.5。我们构建了小鼠4号染色体着丝粒部分跨Wheels区域的遗传和辐射杂交图谱，并将Wheels位点的位置精确到D4 Mit 104和D4 Mit 181之间的类似于1.1-cM的区域。我们将编码Epha 7的基因座置于Wheels候选区域;然而，进一步分析显示Epha 7编码区没有突变，mRNA表达模式也没有可检测到的变化。总之，我们的研究结果表明，车轮，一个对胚胎生存至关重要的基因，可能会连接血管，后脑和内耳发育所涉及的不同过程。(C)北京：科学出版社.
In a screen for mouse mutations with dominant behavioral anomalies, we identified Wheels, a mutation associated with circling and hyperactivity in heterozygotes and embryonic lethality in homozygotes. Mutant Wheels embryos die at E10.5-E11.5 and exhibit a host of morphological anomalies which include growth retardation and anomalies in vascular and hindbrain development. The latter includes perturbation of rhombomeric boundaries as detected by Krox20 and Hoxb1. PECAM-1 staining of embryos revealed normal formation of the primary vascular plexus. However, subsequent stages of branching and remodeling do not proceed normally in the yolk sac and in the embryo proper. To obtain insights into the circling behavior, we examined development of the inner ear by paint-filling of membranous labyrinths of Wh1/+ embryos. This analysis revealed smaller posterior and lateral semicircular canal primordia and a delay in the canal fusion process at E12.5. By E13.5, the lateral canal was truncated and the posterior canal was small or absent altogether. Marker analysis revealed an early molecular phenotype in heterozygous embryos characterized by perturbed expression of Bmp4 and Msx1 in prospective lateral and posterior cristae at E11.5. We have constructed a genetic and radiation hybrid map of the centromeric portion of mouse Chromosome 4 across the Wheels region and refined the position of the Wheels locus to the similar to1.1-cM region between D4Mit104 and D4Mit181. We have placed the locus encoding Epha7, in the Wheels candidate region; however, further analysis showed no mutations in the Epha7-coding region and no detectable changes in mRNA expression pattern. In summary, our findings indicate that Wheels, a gene which is essential for the survival of the embryo, may link diverse processes involved in vascular, hindbrain, and inner ear development. (C) 2001 Academic Press.