RRC ID 4373
Author Kose H, Sakai T, Tsukumo S, Wei K, Yamada T, Yasutomo K, Matsumoto K.
Title Maturational arrest of thymocyte development is caused by a deletion in the receptor-like protein tyrosine phosphatase kappa gene in LEC rats.
Journal Genomics
Abstract 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.
Volume 89(6)
Pages 673-7
Published 2007-6
DOI 10.1016/j.ygeno.2007.03.001
PII S0888-7543(07)00056-0
PMID 17434290
MeSH Animals Animals, Congenic Base Sequence Cell Differentiation Chromosome Mapping DNA, Complementary / genetics Female Humans Male Mice Mice, Inbred C57BL Molecular Sequence Data Organ Culture Techniques Pregnancy Protein Tyrosine Phosphatases / antagonists & inhibitors Protein Tyrosine Phosphatases / genetics* Protein Tyrosine Phosphatases / metabolism RNA Interference Rats Rats, Inbred LEC Sequence Deletion T-Lymphocytes / cytology T-Lymphocytes / immunology T-Lymphocytes / metabolism* Thymus Gland / cytology Thymus Gland / immunology Thymus Gland / metabolism
IF 3.16
Times Cited 11
Rats LEC/Tj(strainID=80) WKAH.LEC-Ptprkthid/Tj(strainID=107)