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首页> 外文期刊>Neoplasia: an international journal for oncology research >A Novel Mouse Model of Diffuse Intrinsic Pontine Glioma Initiated in Pax3-Expressing Cells
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A Novel Mouse Model of Diffuse Intrinsic Pontine Glioma Initiated in Pax3-Expressing Cells

机译：在PAX3表达细胞中引发弥漫性固有斑瘤的一种新型小鼠模型

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Diffuse intrinsic pontine glioma (DIPG) is a rare and incurable brain tumor that arises predominately in children and involves the pons, a structure that along with the midbrain and medulla makes up the brainstem. We have previously developed genetically engineered mouse models of brainstem glioma using the RCAS/Tv-a system by targeting PDGF-B overexpression, p53 loss, and H3.3K27M mutation to Nestin-expressing brainstem progenitor cells of the neonatal mouse. Here we describe a novel mouse model targeting these same genetic alterations to Pax3-expressing cells, which in the neonatal mouse pons consist of a Pax3+/Nestin+/Sox2+ population lining the fourth ventricle and a Pax3+/NeuN+ parenchymal population. Injection of RCAS-PDGF-B into the brainstem of Pax3-Tv-a mice at postnatal day 3 results in 40% of mice developing asymptomatic low-grade glioma. A mixture of low- and high-grade glioma results from injection of Pax3-Tv-a;p53fl/fl mice with RCAS-PDGF-B and RCAS-Cre, with or without RCAS-H3.3K27M. These tumors are Ki67+, Nestin+, Olig2+, and largely GFAP? and can arise anywhere within the brainstem, including the classic DIPG location of the ventral pons. Expression of the H3.3K27M mutation reduces overall H3K27me3 as compared with tumors without the mutation, similar to what has been previously shown in human and mouse tumors. Thus, we have generated a novel genetically engineered mouse model of DIPG, which faithfully recapitulates the human disease and represents a novel platform with which to study the biology and treatment of this deadly disease.
机译：弥漫性内在猪胶质瘤（DIPG）是一种罕见的且无法治愈的脑肿瘤，主要是儿童，并且涉及PON，以及中脑和髓质的结构构成脑干。我们以前通过靶向PDGF-B过表达，P53损失和H3.3K27M突变对新生儿小鼠的巢蛋白的脑干祖细胞来使用RCAS / TV-A系统开发了脑干胶质瘤的脑干胶质瘤的脑干胶质瘤的血管胶囊模型。在这里，我们描述了一种针对PAX3表达细胞的这些相同的遗传改变的新型小鼠模型，其在新生儿小鼠中由衬里第四脑室和PAX3 + / Neun +实质群组成的PAX3 + / Nestin + / Sox2 +群体。将RCAS-PDGF-B注射到PAX3-TV-T TV-TV-T TV的脑干中，在后期3天的小鼠中导致40％的小鼠发育无症状低级胶质瘤。低级和高级胶质瘤的混合物是由注射PAX3-TV-A; P53FL / FL小鼠的用RCAS-PDGF-B和RCAS-CRE，有或没有RCAS-H3.3K27M。这些肿瘤是Ki67 +，Nestin +，Olig2 +，主要是GFAP？并且可以在脑干内的任何地方出现，包括腹侧腹部的经典DIPG位置。与没有突变的肿瘤相比，H3.3K27M突变的表达减少了总体H3K27ME3，类似于先前在人和小鼠肿瘤中所示的内容。因此，我们已经产生了一种新型遗传工程的DIPG小鼠模型，其忠实地概括了人类疾病，并代表了研究这种致命疾病的生物学和治疗的新颖平台。

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