Immunological Phenotyping of Mice with a Point Mutation in Cdk4

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dc.authoridHoyne, Gerard/0000-0002-7370-9139
dc.authorwosidHoyne, Gerard/M-5406-2013
dc.contributor.authorYabas, Mehmet
dc.contributor.authorHoyne, Gerard F.
dc.date.accessioned2024-08-04T20:59:00Z
dc.date.available2024-08-04T20:59:00Z
dc.date.issued2023
dc.departmentİnönü Üniversitesien_US
dc.description.abstractCyclin-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 N-ethyl-N-nitrosourea-induced point mutation in the gene encoding CDK4 on immune cell development. Mutant mice (Cdk4(wnch/wnch)) showed normal development and differentiation of major immune cell subsets in the thymus and spleen. Moreover, T cells from Cdk4(wnch/wnch) mice exhibited normal cytokine production in response to in vitro stimulation. However, analysis of the mixed bone marrow chimeras revealed that Cdk4(wnch/wnch)-derived T cell subsets and NK cells are at a competitive disadvantage compared to Cdk4(+/+)-derived cells in the thymus and periphery of recipients. These results suggest a possible role for the CDK4(wnch) mutation in the development of some immune cells, which only becomes apparent when the Cdk4(wnch/wnch) mutant cells are in direct competition with wild-type immune cells in the mixed bone marrow chimera.en_US
dc.description.sponsorshipThe authors thank the staff of the Australian Phenomics Facility for animal husbandry and genotyping, and Debbie Howard for helping with bone marrow chimera experiments.en_US
dc.description.sponsorshipThe authors thank the staff of the Australian Phenomics Facility for animal husbandry and genotyping, and Debbie Howard for helping with bone marrow chimera experiments.en_US
dc.identifier.doi10.3390/biomedicines11102847
dc.identifier.issn2227-9059
dc.identifier.issue10en_US
dc.identifier.pmid37893220en_US
dc.identifier.urihttps://doi.org/10.3390/biomedicines11102847
dc.identifier.urihttps://hdl.handle.net/11616/103358
dc.identifier.volume11en_US
dc.identifier.wosWOS:001096465700001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherMdpien_US
dc.relation.ispartofBiomedicinesen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectCDK4en_US
dc.subjectT cellsen_US
dc.subjectNK cellsen_US
dc.subjectimmunologyen_US
dc.titleImmunological Phenotyping of Mice with a Point Mutation in Cdk4en_US
dc.typeArticleen_US

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