| First Author | Snyder FF | Year | 1997 |
| Journal | Proc Natl Acad Sci U S A | Volume | 94 |
| Issue | 6 | Pages | 2522-7 |
| PubMed ID | 9122228 | Mgi Jnum | J:39328 |
| Mgi Id | MGI:86711 | Doi | 10.1073/pnas.94.6.2522 |
| Citation | Snyder FF, et al. (1997) Point mutations at the purine nucleoside phosphorylase locus impair thymocyte differentiation in the mouse. Proc Natl Acad Sci U S A 94(6):2522-7 |
| abstractText | Three point mutations on the Np-b allele of the purine nucleoside phosphorylase locus in the mouse have been recovered by male germ cell mutagenesis. The mutants vc ere backcrossed, 12-14 generations, and are designated in increasing order of severity of enzyme deficiency and phenotype: B6-NPE, Met-87-->Lys; B6-NPF, Ala-228-->Thr; and B6-NPG, Trp-1G-->Arg. A marked decline in total cell numbers per thymus occurs between 2 and 3 months for the more severe B6-NPF and B6-NPG mutants (35% and 52%, respectively) and by 8 months for the less severe B6-NPE mutation. The thymocyte population is thereafter characterized by a 3- or 8-fold expanded precursor, CD4(- )CD8(-) double-negative population and 15% or 55% reduced CD4(+)CD8(+) double-positive cells for the B6-NPF and B6- NPG strains, respectively. Spleen lymphocyte Thy-1(+) cells are reduced by 50% and spleen lymphocyte response to T cell mitogen and interleukin 2 is reduced by 80%. Increases of thymocyte dGTP pools of 5- and 2.5 fold for B6-NPF and B6-NPG mutants, respectively, are observed, The purine nucleoside phosphorylase-deficient mouse exhibits age-dependent progressive perturbations in thymocyte differentiation, reduced numbers of thymocytes, and reduced splenic T cell numbers and response. The progressive T cell deficit is similar to the human disorder. |
