Heterozygous Rb-1 delta 20/+mice are predisposed to tumors of the pituitary gland with a nearly complete penetrance

Oncogene. 1994 Apr;9(4):1021-7.

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, alpha-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 10(5) cells. The tumor tissues invariably lose expression of full-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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Animals
  • Biomarkers, Tumor / analysis
  • Chromosome Deletion
  • Disease Susceptibility
  • Genes, Retinoblastoma / genetics*
  • Heterozygote
  • Immunohistochemistry
  • Mice
  • Mice, Mutant Strains
  • Mutation
  • Pituitary Neoplasms / genetics*
  • Pituitary Neoplasms / pathology
  • Retinoblastoma Protein / analysis
  • alpha-MSH / analysis

Substances

  • Biomarkers, Tumor
  • Retinoblastoma Protein
  • alpha-MSH