McNeish J D, Thayer J, Walling K, Sulik K K, Potter S S, Scott W J
Graduate Program in Developmental Biology, University of Cincinnati, Ohio.
J Exp Zool. 1990 Feb;253(2):151-62. doi: 10.1002/jez.1402530205.
In this report, we describe the dysmorphologic phenotype associated with the transgenic insertional mutation legless. This autosomal recessive, perinatally lethal mutation results in an interesting pleiotropic array of congenital malformations. The phenotype of the legless mutation in homozygous perinatal mutants is compared to wild-type nontransgenic and heterozygous siblings. Skeletal, craniofacial, and visceral malformations are characterized. We have observed by skeletal analysis a consistent loss of distal hindlimb structures, as well as the loss of distal forelimb structures with a predilection for the preaxial side of the developing forelimb. Craniofacial malformations commonly observed appear to represent a range of severity of affect, with the mildest manifestation evident as apparently shallow lateral clefts of the upper lip and mild midfacial clefts accompanied by clefts of the secondary palate. At the severe end of the spectrum, the midline clefts of the face (and secondary palate) are very wide, with obvious accompanying frontonasal encephaloceles and overt lateral clefts of the upper lip. Examination of the mutant brain has demonstrated marked defects in the anterior structures, particularly the olfactory lobes and cerebrum, in greater than 90% of the brains studied. Observation of the internal viscera has identified transposition of thoracic and abdominal organs in approximately 50% of the mutant offspring. The limb, head, and visceral defects were not observed in the wild-type nontransgenic or heterozygous siblings. Transgenic insertional mutations leading to congenital malformations are useful because the transgene sequence may serve as a tag to facilitate molecular retrieval. Analysis of the flanking DNA sequences will allow the identification of the interrupted gene. A complete description of the mutant phenotype will assist in the understanding of this genetic locus.
在本报告中，我们描述了与转基因插入突变“无腿”相关的畸形表型。这种常染色体隐性、围产期致死性突变导致了一系列有趣的先天性畸形多效性表现。将纯合围产期突变体中“无腿”突变的表型与野生型非转基因和杂合子同胞进行了比较。对骨骼、颅面和内脏畸形进行了特征描述。通过骨骼分析，我们观察到后肢远端结构持续缺失，以及前肢远端结构缺失，且前肢发育的轴前侧更易受累。常见的颅面畸形似乎代表了一系列不同严重程度的影响，最轻微的表现为上唇明显的浅侧裂和伴有继发腭裂的轻度面中部裂。在严重程度范围的另一端，面部（和继发腭裂）的中线裂非常宽，伴有明显的额鼻脑膨出和明显的上唇外侧裂。对突变体大脑的检查表明，在超过90%的研究大脑中，前部结构，特别是嗅叶和大脑存在明显缺陷。对内脏的观察发现，约50%的突变后代存在胸腹部器官转位。在野生型非转基因或杂合子同胞中未观察到肢体、头部和内脏缺陷。导致先天性畸形的转基因插入突变很有用，因为转基因序列可作为一个标签，便于分子检索。对侧翼DNA序列的分析将有助于识别中断的基因。对突变体表型的完整描述将有助于理解这个基因位点。
