DLX HOMEOBOX GENE CONTROL OF FETAL SKELETOGENESIS

胎儿骨骼形成的 DLX 同源框基因控制

基本信息

批准号：
6719058
负责人：
THOMAS LUFKIN
金额：
$ 22.15万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-04-01 至 2004-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6719058
关键词：
bone development cell differentiation developmental genetics embryo /fetus tissue /cell culture embryogenesis gene expression gene mutation genetic enhancer element genetic models genetic promoter element genetic regulation genetic transcription genetically modified animals histogenesis homeobox genes laboratory mouse phenotype skeletal system

项目摘要

DESCRIPTION (adapted from the Investigator's abstract): Based upon their embryonic expression domains and the preliminary results from the Principal Investigator's gene knockout studies presented below, the Dlx5 and Dlx6 homeobox genes are major directors of morphogenesis and cellular differentiation of the fetal skeleton. Dlx5 and Dlx6 also fall within the candidate critical region for the human split hand/split foot developmental disorder (OMIM 183600), also termed ectrodactyly (Caldwell, 1996; Crackower et al., 1996). As demonstrated below, the Principal Investigator has already made a simultaneous knockout of both Dlx5 and Dlx6 (Dlx5/6). Both genes are located a few kb apart on the chromosome, and a targeted deletion of both genes was deleted simultaneously, since the combined Dlx5 and Dlx6 null mouse cannot be achieved by simple intermating of the individual Dlx5 and Dlx6 knockouts, as the two genes are too closely linked. The limb defects observed closely recapitulate the phenotype of the human split hand/split foot inherited human malformation. Dr. Bruce Gelb, IRPG project 3, is pursuing the human aspect of this work. The remaining Dlx5/6 null phenotype shows a severe dysmorphology of craniofacial, axial and appendicular skeleton. What is unclear at this point, and is the primary focus of this proposal (IRPG project 4) is the following: 1) what the individual contribution of Dlx5 and Dlx65 is to this striking phenotype affecting each major subdivision of the fetal skeleton; 2) what the developmental mode of action is of these two genes; 3) what their position is within the hierarchy of skeletal patterning genes; and 4) what their mechanism is of spatiotemporal embryonic transcriptional regulation.

描述（改编自调查员的摘要）：基于他们的胚胎表达域和主的初步结果研究者的基因敲除研究下面介绍了DLX5和DLX6 同源基因是形态发生和细胞的主要主管胎儿骨骼的分化。 DLX5和DLX6也属于人类拆分/分裂脚发育的候选关键区域疾病（OMIM 183600），也称为偶像性（Caldwell，1996; Cockower et eT Al。，1996）。如下所示，首席调查员已经做出了同时敲除DLX5和DLX6（DLX5/6）。两个基因都位于染色体上的几个KB，两个基因的有针对性缺失是同时删除，因为组合的dlx5和dlx6 null鼠标不能为通过简单的单个DLX5和DLX6敲除，作为这两个基因链接得太紧密。肢体缺陷紧密观察到概括人类分裂的手/脚遗传的人类的表型畸形。 IRPG项目3的Bruce Gelb博士正在追求人类的方面这项工作。其余的DLX5/6空表型显示出严重的畸形学颅面，轴向和阑尾骨骼。目前尚不清楚，这是该提案的主要重点（IRPG项目4）是：1） DLX5和DLX65的个人贡献对此引人注目影响胎儿骨骼每个主要细分的表型； 2）什么发展方式是这两个基因。 3）他们的位置是什么在骨骼图案基因的层次结构中； 4）他们的机制是什么是时空的胚胎转录调节。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Homeobox gene Sax2 deficiency causes an imbalance in energy homeostasis.

同源框基因 Sax2 缺陷会导致能量稳态失衡。

DOI：
10.1002/dvdy.21320
发表时间：
2007
期刊：
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子：
0
作者：
Simon,Ruth;Lufkin,Thomas;Bergemann,AndrewD
通讯作者：
Bergemann,AndrewD

Regulatory genomics: Insights from the zebrafish.

监管基因组学：来自斑马鱼的见解。