ENAMEL MINERAL FORMATION DURING MURINE ODONTOGENESIS

小鼠成牙过程中牙釉质矿物质的形成

• 批准号: 6764258
• 负责人: Carolyn Gibson
• 金额: $ 35.18万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-06-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6764258
• 关键词: RNA splicing; ameloblasts; amelogenin; biological models; biological signal transduction; dental development; dental disorder; dentin; electron microscopy; gene expression; gene targeting; genetically modified animals; hardness; in situ hybridization; infrared spectrometry; laboratory mouse; light microscopy; odontoblasts; phenotype; point mutation; polymerase chain reaction; protein structure function; site directed mutagenesis; tooth enamel; transfection /expression vector; transposon /insertion element

DESCRIPTION (provided by applicant): The amelogenin proteins comprise 90% of the organic component of developing enamel matrix, and these proteins are highly conserved evolutionarily. In order to better understand amelogenin function, we have made a mouse model with a targeted disruption of the amelogenin locus, and this is the first knockout mouse described for a tooth extracellular matrix protein. Null mice have hypoplastic enamel with disorganized prism structure. The amelogenin null female mice can be mated with males that contain various amelogenin expression vectors, and male offspring of this mating will express only the transgene, without having any endogenous amelogenin expression. The model system provides a means to screen the significance of mutations in the amelogenin gene, and for function of amelogenins expressed from alternatively spliced mRNAs. This systematic study avoids the complication of Y-chromosomal amelogenin expression, as the sole murine amelogenin gene is on the X chromosome. The aims are (1) to complete the characterization of the amelogenin null dentition for composition and physical characteristics; (2) to create transgenic mice that express single normal or mutated amelogenin proteins, mate them with the null mice, and analyze teeth of offspring; (3) to evaluate LRAP for signal function in vivo and in vitro; and (4) to ascertain additional consequences of absence of amelogenin in maturative ameloblasts, in reparative dentin and during accelerated eruption

描述（由申请人提供）：釉原蛋白质占发育中釉质基质有机组分的90%，这些蛋白质在进化上高度保守。为了更好地了解釉原蛋白的功能，我们已经建立了一个有针对性地破坏釉原蛋白基因座的小鼠模型，这是第一个描述牙齿细胞外基质蛋白的敲除小鼠。小白鼠的牙釉质发育不全，棱柱结构紊乱。无釉原蛋白的雌性小鼠可以与含有各种釉原蛋白表达载体的雄性小鼠交配，并且这种交配的雄性后代将仅表达转基因，而不具有任何内源性釉原蛋白表达。该模型系统提供了一种方法来筛选釉原蛋白基因突变的意义，并从选择性剪接的mRNA表达的釉原蛋白的功能。这种系统的研究避免了Y染色体釉原蛋白表达的复杂性，因为唯一的鼠釉原蛋白基因位于X染色体上。目的是（1）完成釉原蛋白缺失牙列的组成和物理特性的表征;（2）建立表达单个正常或突变釉原蛋白蛋白的转基因小鼠，将它们与缺失小鼠交配，并分析后代的牙齿;（3）评估LRAP的体内和体外信号功能;以及（4）确定在成熟成釉细胞、修复性牙本质和加速萌出过程中缺乏釉原蛋白的其他后果