GENETICS OF SKULL DEVELOPMENT IN A DOWN SYNDROME MOUSE

各种遗传异常导致颅面缺陷， 这是正常发展模式受到干扰的结果。在这 项目，我们将描述颅面问题与 节段性16三体小鼠（Ts 65 Dn小鼠），其显示剂量 在唐氏症中，许多相同的基因以额外的拷贝存在， 综合征越来越强大的工具可用于遗传 分析和动物模型的开发提供了一个实验 方法来鉴定基因的错误表达时， 会导致颅面畸形这些 动物模型提供了在所有阶段的所有组织的系统访问， 发展这些基因的定位是使用YAC Chr 21亚群剂量失衡的转基因小鼠， 小鼠Chr 16同线区。这项研究的具体目标是： 1)颅面形态学差异的量化 出生时的对照和节段性16三体小鼠; 2）测定 第一个可检测到的形态学的胚胎学时间 正常和三体小鼠之间的差异;和3）评估 特定基因或染色体导致发育不良 在转基因和YAC转基因小鼠中的片段。

A variety of genetic anomalies result in craniofacial defects as a result of perturbations of normal patterns of development. In this project, we will characterize craniofacial problems associated with segmental trisomy 16 mice (Ts65Dn mice) which display dosage imbalance for many of the same genes present at extra copies in Down Syndrome. The increasingly powerful tools available for genetic analysis and animal model development provide an experimental approach to the identification of genes whose misexpression when present in three copies contributes to craniofacial anomalies. These animal models provide systematic access to all tissues at all stages of development. Localization of these genes is accomplished using YAC transgenic mice with dosage imbalance for subsets of Chr21 and the syntenic region of mouse Chr 16. The specific aims of the study are: 1) quantification of the craniofacial morphological differences between control and segmentally trisomy 16 mice at birth; 2) determination of the embryological timing of the first detectable morphological differences between normal and trisomic mice; and 3) assessment of the contribution to maldevelopment of specific genes or chromosome segments in transgenic and YAC transgenic mice.