Pravtcheva D D, Wise T L
Department of Pediatrics, Saint Louis University Health Sciences Center, Missouri 63110, USA.
Genetics. 1996 Dec;144(4):1747-56. doi: 10.1093/genetics/144.4.1747.
Oligosyndactylism (Os) is a radiation-induced mutation on mouse chromosome 8 associated with early postimplantation lethality in homozygotes and abnormal development of the limbs and kidneys in heterozygotes. The recessive lethal effect of Os is due to a mitotic block of the embryonic cells that becomes apparent at the blastocyst stage, but it is not known if the heterozygous effect of Os is due to haploinsufficiency of the gene responsible for the mitotic arrest, or is due to mutation(s) of other gene(s). We have recently described a transgene-induced recessive mutation, 94-A/K, that results in early postimplantation death of the embryos, and we have mapped this mutation to the same region of chromosome 8 where Os has been assigned. On the basis of complementation tests between transgenic and Os/+ mice, in vitro growth characteristics and increased mitotic index of 94-A/K embryos, and molecular structural analysis of 94-A and 94-K transgenic and Os/+ mice, we conclude that the 94-A/K mutation represents a new allele of Os. This insertional mutation should facilitate the isolation of a mammalian gene essential for normal progression of the cell cycle beyond metaphase.
少指（趾）畸形（Os）是小鼠8号染色体上的一种辐射诱导突变，纯合子会出现植入后早期致死，杂合子则会出现四肢和肾脏发育异常。Os的隐性致死效应是由于胚胎细胞在囊胚阶段出现有丝分裂阻滞，但尚不清楚Os的杂合效应是由于负责有丝分裂停滞的基因单倍剂量不足，还是由于其他基因的突变。我们最近描述了一种转基因诱导的隐性突变94 - A/K，它会导致胚胎植入后早期死亡，并且我们已将此突变定位到8号染色体上与Os相同的区域。基于转基因小鼠与Os/+小鼠之间的互补试验、94 - A/K胚胎的体外生长特性和增加的有丝分裂指数，以及对94 - A和94 - K转基因小鼠与Os/+小鼠的分子结构分析，我们得出结论，94 - A/K突变代表Os的一个新等位基因。这种插入突变应有助于分离出对细胞周期中期后正常进展至关重要的哺乳动物基因。
