Heterozygous Rb-1(Δ20)/+ mice are predisposed to tumors of the pituitary gland with a nearly complete penetrance

N. Hu, A. Gutsmann, D. C. Herbert, A. Bradley, W. H. Lee, E. Y.H. Lee

Research output: Contribution to journalArticlepeer-review

234 Scopus citations

Abstract

Humans with a germline mutation of the RB gene are predisposed to retinoblastoma with a 90% penetrance and are at higher risk for other rare tumors. We have established a mouse strain carrying a germ-line mutation of the Rb-1 gene. Here we describe a nearly 100% incidence of spontaneous pituitary tumors which arise in Rb-1 heterozygous mice from ages 2 to 11 months. Histological and immunological analysis indicate that these tumors originate from the intermediate lobe of the pituitary gland, which is a vestigial structure in adult humans. Progression of the tumors can be followed by the elevated level of a specific proteolytic product of pro-opiomelanocortin prohormone, α-melanocyte stimulating hormone, in the circulating blood of the tumor-bearing animals. Multiple foci are frequently seen in the tiny intermediate lobe of the pituitary gland which contains approximately 1.5 x 105 cells. The tumor tissues invariably lose expression of fun-length Rb protein due to loss of the single wild-type Rb-1 allele. The Rb knock out mouse strain provides a unique model for addressing tissue-specific tumor predisposition by inactivation of a ubiquitously expressed tumor suppressor gene.

Original languageEnglish (US)
Pages (from-to)1021-1027
Number of pages7
JournalOncogene
Volume9
Issue number4
StatePublished - 1994
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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