Generation of a conditional null allele for Dmp1 in mouse
Generation of a conditional null allele for Dmp1 in mouse
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DOI：
10.1002/dvg.20370
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发表时间：
2008-02-01
期刊：
影响因子：
1.5
通讯作者：
Mishina, Yuji
中科院分区：
文献类型：
--
作者：
Feng, Jian Q.;Scott, Greg;Mishina, Yuji
牙本质基质蛋白1(DMP1)在人类和小鼠中高度保守，在牙齿、骨骼中高度表达，在脑、肾脏和唾液腺等非骨骼组织中表达较少。在病理学上，DMP1与多种形式的癌症和肿瘤引起的骨软化症有关。小鼠Dmp1基因的常规破坏会导致牙齿和骨骼中牙本质的缺陷，包括低磷性软骨病，以及磷酸盐稳态的异常。人类DMPI突变是导致常染色体隐性遗传性低磷血症性软骨病的原因。为了更好地了解DMP1在不同发育阶段的不同组织中的作用和在病理条件下的作用，我们产生了Dmp1牙状鼠，其中loxP位点位于外显子6的两侧，编码超过80%的DMP1蛋白。我们证明了利用Sox2-Cre的Cre介导的重组，Sox2-Cre是一个在胚胎发育早期在上胚中表达的Cre系，导致基因和蛋白的早期缺失。这些纯合子Cre重组缺失小鼠表现出与常规缺失小鼠相同的表型。该动物模型将有助于揭示DMP1在不同年龄不同组织中的不同作用。
Dentin matrix protein1 (DMP1), highly conserved in humans and mice, is highly expressed in teeth, the skeleton, and to a lesser extent in nonskeletal tissues such as brain, kidney, and salivary gland. Pathologically, DMP1 is associated with several forms of cancers and with tumor-induced osteomalacia. Conventional disruption of the murine Dmp1 gene results in defects in dentin in teeth and in the skeleton, including hypophosphatemic rickets, and abnormalities in phosphate homeostasis. Human DMPI mutations are responsible for the condition known as autosomal recessive hypophosphatemic rickets. For better understanding of the roles of DMP1 in different tissues at different stages of development and in pathological conditions, we generated Dmp1 floxed mice in which loxP sites flank exon 6 that encodes for over 80% of DMP1 protein. We demonstrate that Cre-mediated recombination using Sox2-Cre, a Cre line expressed in epiblast during early embryogenesis, results in early deletion of the gene and protein. These homozygous Cre-recombined null mice display an identical phenotype conventional null mice. This animal model will be useful reveal distinct roles of DMP1 in different tissues at different ages.