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Publication : HD mice: a novel mouse mutant with a specific defect in the generation of CD4(+) T cells.

First Author  Dave VP Year  1998
Journal  Proc Natl Acad Sci U S A Volume  95
Issue  14 Pages  8187-92
PubMed ID  9653162 Mgi Jnum  J:48734
Mgi Id  MGI:1274929 Doi  10.1073/pnas.95.14.8187
Citation  Dave VP, et al. (1998) HD mice: a novel mouse mutant with a specific defect in the generation of CD4(+) T cells. Proc Natl Acad Sci U S A 95(14):8187-92
abstractText  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 gamma delta 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(+)8(low) 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.
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