| 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 |
2007-6-1
|
| 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 |
6.205
|
| Times Cited |
14
|
|
WOS Category
|
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
GENETICS & HEREDITY
|
| Resource |
| Rats |
LEC/Tj(strainID=80)
WKAH.LEC-Ptprkthid/Tj(strainID=107) |
