| الملخص: | Cyclin-dependent kinases (CDKs) play a crucial role in regulation of the mammalian cell cycle. CDK4 and CDK6 control the G1/S restriction checkpoint through their ability to associate with cyclin D proteins in response to growth factor signals. CDK4 deficiency in mice gives rise to a range of endocrine-specific phenotypes including diabetes, infertility, dwarfism, and atrophy of the anterior pituitary. Although CDK6 deficiency can cause thymic atrophy due to a block in the double-negative (DN) to double-positive (DP) stage of T cell development, there are no overt defects in immune cell development reported for CDK4-deficient mice. Here, we examined the impact of a novel <i>N</i>-ethyl-<i>N</i>-nitrosourea-induced point mutation in the gene encoding CDK4 on immune cell development. Mutant mice (<i>Cdk4<sup>wnch/wnch</sup></i>) showed normal development and differentiation of major immune cell subsets in the thymus and spleen. Moreover, T cells from <i>Cdk4<sup>wnch/wnch</sup></i> mice exhibited normal cytokine production in response to in vitro stimulation. However, analysis of the mixed bone marrow chimeras revealed that <i>Cdk4<sup>wnch/wnch</sup></i>-derived T cell subsets and NK cells are at a competitive disadvantage compared to <i>Cdk4<sup>+/+</sup></i>-derived cells in the thymus and periphery of recipients. These results suggest a possible role for the CDK4<sup>wnch</sup> mutation in the development of some immune cells, which only becomes apparent when the <i>Cdk4<sup>wnch/wnch</sup></i> mutant cells are in direct competition with wild-type immune cells in the mixed bone marrow chimera.
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