Lack of augmentation of tumor spectrum or severity in dual heterozygous Men1 and Rb1 knockout mice

K.A. Loffler, C.A. Biondi, M.G. Gartside, M.M. Serewko-Auret, R. Duncan, I.D. Tonks, A.W. Mould, Paul Waring, H.K. Muller, G.F. Kay, N.K. Hayward

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    29 Citations (Scopus)


    To identify possible genetic interactions between themechanisms of tumor suppression of menin and pRb, weintercrossed mice with targeted deletions of Men1 andRb1, and compared tumor development in cohorts ofanimals carrying single or dual mutations of these tumorsuppressorgenes. In mice lacking one copy of Men1,pancreatic islet and anterior pituitary adenomas arecommon. In animals lacking one copy of Rb1, intermediatepituitary and thyroid tumors occur at highfrequency, with less frequent development of pancreaticislet hyperplasia and parathyroid lesions. In mice heterozygousfor both Men1 and Rb1, pancreatic hyperplasiaand tumors of the intermediate pituitary and thyroidoccurred at high frequency. Serum measurements ofcalcium and glucose did not vary significantly betweengenotypic groups. Loss of heterozygosity at the Rb1 locuswas common in pituitary and thyroid tumors, whereas lossof menin was observed in pancreatic and parathyroidlesions. The tumor spectrum in the double heterozygoteswas a combination of pathologies seen in each of theindividual heterozygotes, without decrease in age of onset,indicating independent, non-additive effects of the twomutations. Together with the lack of increased tumorspectrum, this suggests that menin and pRbfunct ion in acommon pathway of tumor suppression.
    Original languageEnglish
    Pages (from-to)4009-4017
    Issue number27
    Publication statusPublished - 2007


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