Heterozygous Rb-1 delta 20/+mice are predisposed to tumors of the pituitary gland with a nearly complete penetrance.
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.
Hu
N
N
Center for Molecular Medicine/Institute of Biotechnology, University of Texas, San Antonio 78284.
Gutsmann
A
A
Herbert
D C
DC
Bradley
A
A
Lee
W H
WH
Lee
E Y
EY
D000367:Age Factors; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002872:Chromosome Deletion; D004198:Disease Susceptibility; D016161:Genes, Retinoblastoma / Q000235:genetics*; D006579:Heterozygote; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology; D016160:Retinoblastoma Protein / Q000032:analysis; D000521:alpha-MSH / Q000032:analysis
D014408:Biomarkers, Tumor; D016160:Retinoblastoma Protein; D000521:alpha-MSH