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MESODERMAL HOMEODOMAIN PROTEIN DURING VERTEBRAL DEVELOPMENT

MESODERMAL HOMEODOMAIN PROTEIN DURING VERTEBRAL DEVELOPMENT
椎骨发育过程中的中胚层同源域蛋白
批准号:
6163105
负责人:
H ARNHEITER
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至

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中文摘要
翻译
带有Meox1中胚层转基因插入突变的小鼠 11号染色体上的同源区域转录因子基因出现异常 在包括颅椎融合在内的轴向骨骼中,椎骨- 脊柱融合、半椎体和椎源性脊柱裂。这些 所有的表型都可以追溯到发育过程中的异常 Sklerotome。近亲Meox2,尽管最初与Meox2共表达 显然,Meox1不能弥补Meox1的缺失。然而,即使是 虽然缺乏Meox2本身与生命是相容的,但小鼠 我们的Meox1等位基因纯合和Meox2基因敲除的等位基因严重 在合作努力中表现出来的受影响的。因此,Meox1和Meox2 是两个相关的中胚层同源结构域转录因子,必须 合作建立复杂的轴向骨架图案。 有趣的是,纯合子的Meox1突变女性不能分泌乳汁,因为 妊娠晚期乳腺发育的缺陷。这是不是 哺乳缺陷是由于间质或上皮缺陷所致。 正在接受乳腺移植的调查。自.以来 转基因插入导致基因组DNA的缺失超过了 Meox1基因的3‘端,有可能是骨骼表型 和/或乳腺表型是由于一个或多个 另外一个基因位于Meox1附近。因此,我们有 开始尝试拯救带有Meox1基因的突变小鼠,使用 基于YAC的转基因策略。
英文摘要
Mice with a transgenic insertional mutation in the Meox1 mesodermal homeodomain transcription factor gene on chromosome 11 show abnormalities in the axial skeleton including cranio-vertebral fusions, vertebro- vertebral fusions, hemivertebrae, and a vertebrogenic spina bifida. These phenotypes can all be traced back to abnormalities in the developing sklerotome. A close relative, Meox2, though initially coexpressed with Meox1, evidently cannot compensate for the lack of Meox1. However, even though the lack of Meox2 alone is compatible with life, mice doubly homozygous for our Meox1 allele and a Meox2 knock-out allele are severely affected as demonstrated in a collaborative effort. Thus, Meox1 and Meox2 are two related mesodermal homeodomain transcription factors that must collaborate to establish the intricate patterning of the axial skeleton. Interestingly, homozygous Meox1 mutant females cannot lactate because of a defect in mammary gland development during late pregnancy. Whether this lactation defect is due to a stromal or an epithelial defect is currently being investigated by mammary gland transplantations. Since the transgenic insertion has resulted in a deletion of genomic DNA beyond the 3' end of the Meox1 gene, it is possible that the skeletal phenotype and/or the mammary gland phenotype are due to effects on one or more than one additional gene located in the vicinity of Meox1. Therefore, we have initiated attempts to rescue the mutant mice with a Meox1 cDNA, using a YAC-based transgenic strategy.
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ANALYSIS OF INSERTIONAL MUTATIONS IN TRANSGENIC MICE
BIOLOGY OF MAMMALIAN HOMEODOMAIN PROTEINS
ANALYSIS OF INSERTIONAL MUTATIONS IN TRANSGENIC MICE
ANALYSIS OF INSERTIONAL MUTATIONS IN TRANSGENIC MICE
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