title: Extensive contribution of Rb-deficient cells to adult chimeric mice with limited histopathological consequences.
abstract: Homozygosity for a mutation in the Rb tumor suppressor gene causes mid-gestation embryonic lethality in the mouse. Using a two-step targeting protocol, we have constructed Rb homozygous mutant mouse embryonic stem cells and used them to create chimeric animals partially composed of Rb-deficient cells. Analysis of these chimeras demonstrates widespread contribution of the mutant cells to adult tissues, including the retina and mature erythrocytes. Despite the presence of large numbers of Rb-deficient cells in most tissues of these mice, they are remarkably normal but do exhibit certain histological defects including cataracts, hyperplasia of the adrenal medulla, and enlarged cells in the cerebellum and the liver. Like animals heterozygous for the Rb mutation, the chimeras develop tumors of the intermediate lobe of the pituitary, and the rate of pituitary tumorigenesis is greatly accelerated.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
authors.forename: B O
authors.initials: BO
authors.lastname: Williams
authors.forename: E M
authors.initials: EM
authors.lastname: Schmitt
authors.forename: L
authors.initials: L
authors.lastname: Remington
authors.forename: R T
authors.initials: RT
authors.lastname: Bronson
authors.forename: D M
authors.initials: DM
authors.lastname: Albert
authors.forename: R A
authors.initials: RA
authors.lastname: Weinberg
authors.forename: T
authors.initials: T
authors.lastname: Jacks
mesh_terms: D000311:Adrenal Glands / Q000473:pathology; D000818:Animals; D001755:Blastocyst; D004920:Erythropoiesis; D005123:Eye / Q000473:pathology; D005804:Genes, Lethal / Q000235:genetics*; D016161:Genes, Retinoblastoma / Q000235:genetics*; D005956:Glucose-6-Phosphate Isomerase / Q000032:analysis; D006720:Homozygote; D007527:Isoenzymes / Q000032:analysis; D051379:Mice; D009154:Mutation; D010902:Pituitary Gland / Q000473:pathology; D010911:Pituitary Neoplasms / Q000235:genetics; D016160:Retinoblastoma Protein / Q000172:deficiency* / Q000235:genetics; D013234:Stem Cells; D018183:Transplantation Chimera
chemical_list: D007527:Isoenzymes; D016160:Retinoblastoma Protein; D005956:Glucose-6-Phosphate Isomerase