Maturational arrest of thymocyte development is caused by a deletion in the receptor-like protein tyrosine phosphatase kappa gene in LEC rats.
The Long-Evans Cinnamon (LEC) rat has a spontaneous mutation, T helper immunodeficiency (thid), which causes a markedly reduced CD4(+) thymocyte population. Here we positionally clone the locus and identify a deletion in the gene encoding a receptor-like protein tyrosine phosphatase kappa (Ptprk) that led to complete loss of the transcript. The rat Ptprk gene exhibits 98% identity with the human and mouse counterparts and is expressed most abundantly in the CD4(-)CD8(-) double-negative stage. The downregulation of Ptprk in mouse immature thymocytes by RNA interference mimicked the thid phenotype. These results indicate that thid maps to the Ptprk locus and that functional Ptprk is crucial for lineage commitment or progression of CD4(+) T cells. We also found that Ptprk appears to function in parallel with or downstream of Th-POK/cKrox (also known as ZBTB7B), a master regulator of T cell lineage decision.
Kose
Hiroyuki
H
Division of Animal Research Resources, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
Sakai
Tohru
T
Tsukumo
Shin-ichi
S
Wei
Kaichun
K
Yamada
Takahisa
T
Yasutomo
Koji
K
Matsumoto
Kozo
K
D000818:Animals; D020296:Animals, Congenic; D001483:Base Sequence; D002454:Cell Differentiation; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D011247:Pregnancy; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D020332:Rats, Inbred LEC; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D018076:DNA, Complementary; D017027:Protein Tyrosine Phosphatases