High-resolution mapping of the truncate (tc) locus on mouse chromosome 6.
High-resolution mapping of the truncate (tc) locus on mouse chromosome 6.
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小鼠 6 号染色体上截短 (tc) 基因座的高分辨率图谱。
DOI：
10.1007/s003359900879
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Gossler,A
中科院分区：
文献类型：
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作者：
Pavlova,MN;Clark,AM;Gossler,A
在胚胎发育过程中，脊索在中轴胚层结构和中枢神经系统的形成中起着关键作用。脊索的缺陷会导致轴骨和脊髓的畸形或发育不全。虽然脊索的功能已经确定，但人们对控制其发育和完整性并因此影响图案形成过程的遗传因素知之甚少。为了了解脊索发育和完整性的时空差异的分子机制，分离和鉴定参与这些过程的基因是必不可少的。在小鼠中，已经在五个基因中发现了特定扰乱脊索发育和/或完整性的自发突变(Johnson 1986；Theler 1988)。这些突变在胚胎发育的不同时间以及在体轴前后的不同位置对脊索发育有特定的影响。到目前为止，只有一个受影响的基因brachyury被克隆并在分子水平上进行了分析(Herrmann等人)。1990年)。在剩下的突变中，到目前为止，它们的分子性质和受影响的基因都还没有确定。‘截断’是一种隐性突变，不完全外显，只影响脊索的后部(Theler 1957,1959)。纯合子D9。5-D10胚胎，脊索不能尾部生长并突然终止，通常在骶骨区域。在缺乏脊索的区域，上覆的神经管中没有底板发育，体节跨中线融合，硬结发育受阻。这些异常会导致TC纯合子突变的尾部、骶骨和/或腰椎区域的脊柱畸形和/或发育不全。在最严重的情况下，后腿瘫痪，脊髓底板和正中腹裂缺失。TC突变胚胎中的特殊缺陷表明截断是正常脊索形成所必需的基因，特别是在体轴的尾部区域。因此，TC基因的分离和分子特征可能有助于阐明脊索发育的机制。Truncate先前已被证明基于它与WA1的连锁将其映射到染色体(Chr)6(Robinson 1972)，WA1与转化生长因子α等位(Luetteke等人)。1993)和Mitfmi。然而，Mitfmi和WA1是唯一用于定位TC的标记。在这篇文章中，我们提出了一个围绕TC基因的详细遗传连锁图谱，作为TC基因定位克隆的第一步。
The notochord plays a pivotal role in patterning axial mesodermal structures and the central nervous system during embryogenesis. Defects in the notochord lead to malformations or agenesis of the axial skeleton and of the spinal cord. Whereas the functions of the notochord are well established, little is known about the genetic elements that control its development and integrity, and thus influence pattern-forming processes. To understand the molecular mechanisms underlying the temporal and spatial differences of notochord development and integrity, the isolation and functional characterization of genes involved in these processes is essential. In mice, spontaneous mutations that specifically perturb the development and/or integrity of the notochord have been identified in five genes (Johnson 1986; Theiler 1988). These mutations have specific effects on notochord development at different times during embryogenesis and at different positions along the anteriorposterior body axis. To date, only one of the affected genes, brachyury, has been cloned and analyzed on the molecular level (Herrmann et al. 1990). In the case of the remaining mutations, neither their molecular nature nor the affected genes have been characterized thus far.‘‘truncate’’is a recessive mutation with incomplete penetrance affecting exclusively the posterior portion of the notochord (Theiler 1957, 1959). In homozygous d9. 5-d10 embryos, the notochord fails to grow caudally and abruptly ends, usually in the sacral region. In the region lacking the notochord, no floorplate develops in the overlying neural tube, somites fuse across the midline, and sclerotome development is impaired. These abnormalities lead to malformations and/or agenesis of the vertebral column in the tail, the sacrum and/or the lumbar region of homozygous tc mutants. In the most severe cases, the hind legs are paralyzed and the floor plate and median ventral fissure of the spinal cord is absent. The anterior notochord remains fully intact and is not affected by this mutation.The specific defects in tc mutant embryos suggest that truncate is an essential gene required for normal notochord formation, specifically, in the caudal region of the body axis. Thus, the isolation and molecular characterization of the tc gene is likely to elucidate the mechanisms governing notochord development. truncate has previously been shown to map to Chromosome (Chr) 6 (Robinson 1972) based on its linkage with wa1, which is allelic with Tgfα (Luetteke et al. 1993) and Mitfmi. However, Mitfmi and wa1 were the only markers used to map tc. In this paper we present a detailed genetic linkage map around the tc locus as a first step towards the positional cloning of the tc gene.