Rinchik E M
Biology Division, Oak Ridge National Laboratory, Tennessee 37831-8077.
Genetics. 1994 Jul;137(3):855-65. doi: 10.1093/genetics/137.3.855.
Numerous new mutations at the brown (b) locus in mouse chromosome 4 have been recovered over the years in germ-cell mutagenesis experiments performed at the Oak Ridge National Laboratory. A large series of radiation- and chemical-induced b mutations known to be chromosomal deletions, and also known to be prenatally lethal when homozygous, were analyzed by pairwise complementation crosses as well as by pseudodominance tests involving flanking loci defined by externally visible phenotypes. These crosses were designed to determine the extent of each deletion on the genetic and phenotype map of the chromosomal region surrounding the b locus; the crosses also provided basic data that assigned deletions to complementation groups and defined four new loci associated with aberrancies in normal development. Specifically, the pseudodominance tests identified deletions that include the proximally mapping whirler (wi) and the distally mapping depilated (dep) genes, thereby bracketing these loci defined by visible developmental abnormalities with landmarks (deletion breakpoints) that are easily identified on the physical map. Furthermore, the complementation crosses, which were supplemented with additional crosses that allowed determination of the gross time of lethality of selected deletions, defined four new loci required for normal development. Homozygous deletion of one of these loci (b-associated fitness, baf) results in a runting syndrome evident during postnatal development; deletion of one locus [l(4)2Rn] causes death in the late gestation/neonatal period; and deletion of either of two loci [l(4)1Rn or l(4)3Rn] results in embryonic death, most likely in pre-, peri- or postimplantation stages. The placement of these new functionally defined loci on the evolving molecular map of the b region should be useful for continuing the analysis of the roles played in development by genes in this segment of chromosome 4.
多年来，在橡树岭国家实验室进行的生殖细胞诱变实验中，已在小鼠4号染色体的棕色（b）位点发现了许多新突变。通过成对互补杂交以及涉及由外部可见表型定义的侧翼位点的拟显性测试，对一系列已知为染色体缺失且纯合时产前致死的辐射和化学诱导的b突变进行了分析。这些杂交旨在确定每个缺失在b位点周围染色体区域的遗传和表型图谱上的范围；这些杂交还提供了基础数据，将缺失分配到互补组，并定义了四个与正常发育异常相关的新位点。具体而言，拟显性测试确定了包括近端定位的旋转（wi）和远端定位的脱毛（dep）基因的缺失，从而用在物理图谱上易于识别的界标（缺失断点）将由可见发育异常定义的这些位点括起来。此外，互补杂交辅以额外的杂交，从而能够确定所选缺失的致死大致时间，定义了正常发育所需的四个新位点。其中一个位点（b相关适应性，baf）的纯合缺失导致产后发育期间明显的发育迟缓综合征；一个位点[l(4)2Rn]的缺失导致妊娠后期/新生儿期死亡；两个位点[l(4)1Rn或l(4)3Rn]中的任何一个缺失都会导致胚胎死亡，最有可能发生在植入前、植入时或植入后阶段。将这些新的功能定义位点定位在不断发展的b区域分子图谱上，应有助于继续分析4号染色体这一片段中的基因在发育中所起的作用。
