Mutations in the osteopetrotic transmembrane protein 1 (Ostm1) gene are responsible for the most severe form of autosomal recessive osteopetrosis both in humans and in the gray lethal (gl/gl) mouse. This defect leads to increased bone mass with bone marrow occlusion and hematopoietic defects. To establish the expression profile of the mouse Ostm1 protein in vivo, homologous recombination in bacteria was designed to generate a V5‐Ostm1 bacterial artificial chromosome (BAC) that was subsequently integrated in the mouse genome. Tissue expression of the transgene V5‐Ostm1 RNA and protein in transgenic mice follow the endogenous expression profile. Immunohistochemistry analysis demonstrated expression in neuronal populations from central and peripheral nervous system and defined a unique cellular expression pattern. Importantly, together with appropriate protein post‐translational modification, in vivo rescue of the osteopetrotic bone gl/gl phenotype in BAC V5‐Ostm1 gl/gl mice is consistent with the expression of a fully functional and active protein. These mice represent a unique tool to unravel novel Ostm1 functions in individual tissue and neuronal cell populations and the V5‐Ostm1 transgene represents an easy visual marker to monitor the expression of Ostm1 in vitro and in vivo.

中文翻译：

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V5-Ostm1蛋白在细菌人工染色体转基因小鼠中的表达模式

骨硬化跨膜蛋白 1 ( Ostm1 ) 基因的突变是导致人类和灰色致死性 ( gl / gl ) 常染色体隐性遗传性骨硬化症最严重形式的原因。） 老鼠。这种缺陷导致骨髓阻塞和造血缺陷导致骨量增加。为了建立小鼠 Ostm1 蛋白在体内的表达谱，设计了细菌中的同源重组以产生随后整合到小鼠基因组中的 V5-Ostm1 细菌人工染色体 (BAC)。转基因 V5-Ostm1 RNA 和蛋白质在转基因小鼠中的组织表达遵循内源性表达谱。免疫组织化学分析证明了在中枢和外周神经系统的神经元群体中的表达，并定义了独特的细胞表达模式。重要的是，与适当的蛋白质翻译后修饰一起，体内拯救BAC V5-Ostm1中的骨硬化骨gl / gl表型gl / gl小鼠的表达符合一种功能齐全的活性蛋白。这些小鼠代表了一种独特的工具，可以在单个组织和神经元细胞群中揭示新的 Ostm1 功能，而 V5-Ostm1 转基因代表了一种简单的视觉标记，可以在体外和体内监测 Ostm1 的表达。