The V–J Recombination of T Cell Receptor-γ Genes Is Blocked in Interleukin-7 Receptor–deficient Mice
نویسندگان
چکیده
IL-7R-deficient mice have severely impaired expansion of early lymphocytes and lack gamma delta T cells. To elucidate the role of IL-7R on gamma delta T cell development, we analyzed the rearrangements of TCR-alpha, beta, gamma, and delta genes in the thymus of the IL-7R-deficient mice. Southern blot analysis with a J gamma 1 probe revealed that more than 70% of J gamma 1 and J gamma 2 alleles are recombined to form distinct V gamma 1.2-J gamma 2 and V gamma 2-J gamma 1 fragments in control mice. On the contrary, no such recombination was detected in the mutant mice. The rearrangements in the TCR-alpha, beta, and delta loci were comparably observed in control and mutant mice. PCR analysis indicated that the V-J recombination of all the V gamma genes is severely hampered in the mutant mice. The mRNA of RAG-1, RAG-2, Ku-80, and terminal deoxynucleotidyl transferase (TdT) genes was equally detected between control and mutant thymi, suggesting that the expression of common recombination machinery is not affected. These data demonstrated that the V-J recombination of the TCR gamma genes is specifically blocked in the IL-7R-deficient mice and suggested the presence of highly specific regulation for TCR gamma gene rearrangement.
منابع مشابه
Expression of Recombination Activating Genes in Germinal Center B Cells: Involvement of Interleukin 7 (IL-7) and the IL-7 Receptor
Mouse germinal center (GC) B cells have been shown to undergo secondary V(D)J (V, variable; D, diversity; J, joining) recombination (receptor editing) mediated by the reexpressed products of recombination activating gene (RAG)-1 and RAG-2. We show here that interleukin (IL)-7 as well as IL-4 was effective in inducing functional RAG products in mouse IgD+ B cells activated via CD40 in vitro. Blo...
متن کاملThe Interleukin 7 Receptor Is Required for T Cell Receptor γ Locus Accessibility to the V(D)j Recombinase
Defects in the interleukin (IL)-7 signal transduction pathway lead to severe immunodeficiency in humans and in mice. In IL-7 receptor-deficient (IL-7R-/-) mice, lymphoid precursors show a reduced survival rate and variable/diversity/joining region V(D)J recombination is variously affected in different loci, being arrested in the T cell receptor (TCR)-gamma locus, aberrant in the immunoglobulin ...
متن کاملDefective Development of γ/δ T Cells in Interleukin 7 Receptor–Deficient Mice Is Due to Impaired Expression of T Cell Receptor γ Genes
Mice lacking the interleukin 7 receptor (IL-7R) generate alpha/beta T cells at a detectable but greatly reduced rate, but gamma/delta T cells are completely absent. The special role of IL-7R signaling in gamma/delta T cell development has remained unclear. IL-7Ralpha(-/-) mice exhibit a paucity of gamma gene rearrangements. This striking observation can be explained by a defect in T cell recept...
متن کاملProtective effect of interleukin-36 receptor antagonist on liver injury induced by concanavalin A in mice
Objective(s): Interleukin-36 receptor antagonist (IL-36Ra) is a new member of the IL-1 family that exhibits anti-inflammatory activity in a variety of inflammatory and immune diseases. Our purpose was to determine the effect of IL-36Ra on liver injury in a mouse hepatitis model induced by concanavalin A (ConA). Materials and Methods: Mic...
متن کاملAllantoin improves methionine-choline deficient diet-induced nonalcoholic steatohepatitis in mice through involvement in endoplasmic reticulum stress and hepatocytes apoptosis-related genes expressions
Objective(s): Non-alcoholic steatohepatitis (NASH) is defined by steatosis and inflammation in the hepatocytes, which can progress to cirrhosis and possibly hepatocellular carcinoma. However, current treatments are not entirely effective. Allantoin is one of the principal compounds in many plants and an imidazoline I receptor agonist as well. Allantoin has positive eff...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- The Journal of Experimental Medicine
دوره 184 شماره
صفحات -
تاریخ انتشار 1996