A deletion mutation of the protein tyrosine phosphatase kappa (Ptprk) gene is responsible for T-helper immunodeficiency (thid) in the LEC rat.
Bone marrow (BM)-derived T-cell progenitors differentiate into CD4 or CD8 single-positive (SP) cells in the thymus. We have previously reported that a single autosomal mutation, thid, causes a defect in the maturation of CD4 SP thymocytes and an abnormality of peripheral helper T cells in the LEC rat. In this study we attempted to identify a gene responsible for the thid mutation. We first performed genetic linkage analysis and mapped the thid locus between Myb and D1Rat392 on Chr 1. In this region we found an approximately 380-kb deletion from intron 3 of the Ptprk gene, which encodes a receptor-like protein tyrosine phosphatase type kappa (RPTPkappa) to intron 1 of the RGD1560849 predicted gene in the LEC rat genome. Reconstitution with syngenic BM cells transduced Ptprk but not the RGD1560849 predicted gene rescued development of CD4 SP cells in the LEC rat thymus. It is confirmed by this result that the Ptprk gene is responsible for the thid mutation in the LEC rat. Our results further suggest that RPTPkappa plays a critical role in the development of CD4 SP cells in the thymus.
Asano
Atsushi
A
Laboratory of Experimental Animal Science, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Kita-18, Nishi-9, Kita-ku, Sapporo 060-0818, Japan.
Tsubomatsu
Kouta
K
Jung
Cha-Gyun
CG
Sasaki
Nobuya
N
Agui
Takashi
T
D000818:Animals; D001483:Base Sequence; D016026:Bone Marrow Transplantation; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology* / Q000235:genetics* / Q000276:immunology; D007438:Introns; D008297:Male; D016133:Polymerase Chain Reaction; D051381:Rats; D020332:Rats, Inbred LEC / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics*; D017384:Sequence Deletion; D006377:T-Lymphocytes, Helper-Inducer / Q000201:enzymology* / Q000276:immunology*; D014161:Transduction, Genetic; D014185:Transplantation, Isogeneic
D017931:DNA Primers; D004247:DNA; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2