Characterization of neuroendocrine tumors in heterozygous mutant MENX rats: a novel model of invasive medullary thyroid carcinoma [pituitary]

As overwhelming evidence coming from transgenic mouse models but also from MEN4 patients seem to suggest that loss or inactivation of a single p27 allele plays an important role in neuroendocrine tumorigenesis, we decided to perform a detailed analysis of the phenotype of rats heterozygous for the MENX-associated germline Cdkn1b mutation. We here show that the reduction to a single functional p27 allele predisposes MENX heterozygous rats to the development of neuroendocrine malignancies.鉴于转基因小鼠模型以及MEN4（多发性内分泌腺瘤4型，Multiple Endocrine Neoplasia Type 4）患者的大量研究证据均表明，单个p27等位基因的缺失或失活在神经内分泌肿瘤发生过程中发挥重要作用，本研究遂对携带MENX（多发性内分泌腺瘤X型，Multiple Endocrine Neoplasia Type X）相关生殖系Cdkn1b（细胞周期蛋白依赖性激酶抑制剂1B，Cyclin-Dependent Kinase Inhibitor 1B）突变的杂合大鼠的表型开展详细分析。研究结果显示，仅保留单个功能性p27等位基因的MENX杂合大鼠，易发生神经内分泌恶性肿瘤。