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

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. We compared 2 different groups: adrenal gland from wild type rats and adrenal lesions from heterozygous p27Kip1/Cdknb1 mutant rats.