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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >POINT MUTATIONS AT THE PURINE NUCLEOSIDE PHOSPHORYLASE LOCUS IMPAIR THYMOCYTE DIFFERENTIATION IN THE MOUSE
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POINT MUTATIONS AT THE PURINE NUCLEOSIDE PHOSPHORYLASE LOCUS IMPAIR THYMOCYTE DIFFERENTIATION IN THE MOUSE

机译：嘌呤核苷磷酸酶基因位点的突变削弱小鼠胸腺细胞的分化。

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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. [References: 49]
机译：雄性生殖细胞诱变已恢复小鼠嘌呤核苷磷酸化酶基因座Np-b等位基因上的三个点突变。 vc突变体回交了12-14代，并以酶缺乏和表型的严重性的升序排列：B6-NPE，Met-87-> Lys； B6-NPF，Ala-228-> Thr；和B6-NPG，Trp-1G-> Arg。对于较严重的B6-NPF和B6-NPG突变体（分别为35％和52％），每个胸腺的总细胞数显着下降在2到3个月之间，而对于较不严重的B6-NPE突变，每个胸腺的总细胞数出现8个月的下降。此后，胸腺细胞群体的特征是3倍或8倍扩增的前体，CD4（-）CD8（-）双阴性群体和15％或55％减少的CD4（+）CD8（+）双阳性细胞。 B6-NPF和B6-NPG菌株。脾淋巴细胞Thy-1（+）细胞减少了50％，脾淋巴细胞对T细胞促分裂原和白介素2的反应减少了80％。对于B6-NPF和B6-NPG突变体，分别观察到胸腺细胞dGTP池增加了5倍和2.5倍。嘌呤核苷磷酸化酶缺陷型小鼠在胸腺细胞分化中表现出年龄依赖性进行性扰动，胸腺细胞数量减少，并且减少脾T细胞数量和反应。进行性T细胞缺乏症与人类疾病相似。 [参考：49]

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