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HD mice: A novel mouse mutant with a specific defect in the generation of CD4+ T cells

By Vibhuti P. Dave, David Allman, Robert Keefe, Richard R. Hardy and Dietmar J. Kappes

Abstract

We have identified a spontaneous mutation in mice, which we term HD for “helper T cell deficient.” This mouse is distinguished by the virtual absence of peripheral T cells of the CD4+8− major histocompatibility complex (MHC) class II-restricted T helper subset due to a specific block in thymic development. The developmental defect is selective for CD4+8− cells; the maturation of CD4−8+ and γδ T cells is normal. The autosomal recessive mutation underlying the HD phenotype is unrelated to MHC class II, since it segregates independently of the MHC class II locus. Moreover, the HD phenotype is not caused by a defect of the CD4 gene. Bone marrow transfer experiments demonstrate that the defect is intrinsic to cells of the hematopoietic lineage, i.e., most likely to developing thymocytes themselves. The frequency of CD4+8low intermediate cells is markedly increased in HD mice, suggesting that class II-restricted thymocytes are arrested at this stage. This is the first genetic defect of its kind to be described in the mouse and may prove highly informative in understanding the molecular pathways underlying lineage commitment

Topics: Biological Sciences
Publisher: The National Academy of Sciences
Year: 1998
OAI identifier: oai:pubmedcentral.nih.gov:20951
Provided by: PubMed Central
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