The nonobese diabetic scid mouse: model for spontaneous thymomagenesis associated with immunodeficiency.
Homozygosity for the severe combined immunodeficiency (scid) mutation results in a block in T- and B-lymphocyte development. An unusually high incidence of spontaneous thymic lymphoma development was observed after transfer of this mutation from the C.B-17 congenic strain background onto the diabetes-susceptible nonobese diabetic (NOD) background. Thymomagenesis in the NOD-scid/scid mouse was associated with expression of an NOD mouse-unique endogenous ecotropic murine leukemia provirus locus (Emv-30, mapped to proximal region of chromosome 11) not expressed in the standard substrain NOD/Lt thymus. All tumors exhibited insertions of ecotropic proviruses, whereas only a subset also exhibited proviral integrations of mink cell focus-forming retrovirus. Neither class of retrovirus was associated with consistent integration into genes previously associated with activation of oncogenesis. We propose that the unusual features of T-cell ontogeny characteristic of the NOD inbred strain synergize with the scid-imparted block in thymocyte development, leading to activation of the NOD-unique Emv-30 to initiate thymomagenesis.
Jackson Laboratory, Bar Harbor, ME 04609.
M
M
Prochazka
H R
HR
Gaskins
L D
LD
Shultz
E H
EH
Leiter
D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D009052:Leukemia Virus, Murine / Q000235:genetics; D008223:Lymphoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD / Q000235:genetics; D016513:Mice, SCID / Q000235:genetics*; D010641:Phenotype; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D013950:Thymus Gland / Q000002:abnormalities*; D013953:Thymus Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016662:Virus Integration
D004273:DNA, Neoplasm; D012313:RNA