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. 1992 Apr 15;89(8):3290–3294. doi: 10.1073/pnas.89.8.3290

The nonobese diabetic scid mouse: model for spontaneous thymomagenesis associated with immunodeficiency.

M Prochazka 1, H R Gaskins 1, L D Shultz 1, E H Leiter 1
PMCID: PMC48852  PMID: 1373493

Abstract

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.

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Selected References

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