Mutations in the Recombination Activating Gene 1 (RAG1) can cause a wide variety of clinical and immunological phenotypes in humans, ranging from absence of T and B lymphocytes to occurrence of autoimmune manifestations associated with expansion of oligoclonal T cells and production of autoantibodies. Although the mechanisms underlying this phenotypic heterogeneity remain poorly understood, som...

Resistance to angiotensin II (Ang II)-induced hypertension in T-cell-deficient male mice with a targeted mutation in the recombination-activating gene-1 (Rag1) on the C57BL/6J background (B6.Rag1-/- -M), which was reported by 5 independent laboratories including ours before 2015, has been lost. In mice purchased from Jackson Laboratory in 2015 and 2016, the time course and magnitude increase in...

BACKGROUND Coeliac disease is a small intestine enteropathy caused by permanent intolerance to wheat gluten. Gluten intake by patients with coeliac disease provokes a strong reaction by intestinal intraepithelial lymphocytes (IELs), which normalises on a gluten-free diet. AIM To investigate whether impaired extrathymic T cell maturation and/or secondary T cell receptor (TCR) gene recombinatio...

To study B-cell development from bone marrow (BM), we generated recombination-activating gene 1 (Rag1)-targeted mice lacking mature lymphocytes. B-cell development can be induced in such mice by B cell-specific restoration of a functional Rag1 transcription unit. Follicular and marginal zone B cells populated the spleen when Rag1 expression was permitted. Notably, the peritoneal cavity was domi...

When naïve T cells reconstitute lymphopenic hosts, they transiently proliferate and differentiate into memory-like T cells. Here we report that tumor-specific T cells preferentially expand in tumor vaccine-draining lymph nodes after a melanoma vaccine given to RAG1 mice reconstituted with naïve T cells from normal mice. The percentage of tumor-specific Tc1 T cells detected by intracellular cyto...

Development of a small animal model for the in vivo study of human immunity and infectious disease remains an important goal, particularly for investigations of HIV vaccine development. NOD/Lt mice homozygous for the severe combined immunodeficiency (Prkdc scid) mutation readily support engraftment with high levels of human hematolymphoid cells. However, NOD/LtSz-scid mice are highly radiosensi...

OBJECTIVE Natural killer (NK) cells have been identified in human vascular pathologies. In this study, we identified NK cells in aortic root atherosclerotic lesions of low density lipoprotein (LDL) receptor-deficient (LDLr-/-) mice. To characterize the role of NK cell-mediated cytolysis in atherosclerosis, we generated C57Bl/6 double-mutant mice by crossing LDLr-/- mice with NK cell-defective L...

Recombination-activating gene 1 protein (RAG1) and RAG2 are critical enzymes for initiating variable-diversity-joining (VDJ) segment recombination, an essential process for antigen receptor expression and lymphocyte development. The transcription factor BCL11A is required for B cell development, but its molecular function(s) in B cell fate specification and commitment is unknown. We show here t...

Background: Celiac disease (CD) is a small intestine enteropathy caused by permanent wheat gluten intolerance. Gluten intake by CD patients provokes a strong reaction by intestinal intraepithelial lymphocytes (IELs), which normalizes on a gluten-free diet. Aim: To investigate whether impaired extrathymic T cell maturation and/or secondary T cell receptor (TCR) gene recombination in IELs are fea...

BACKGROUND Universal nuclear protein-coding locus (NPCL) markers that are applicable across diverse taxa and show good phylogenetic discrimination have broad applications in molecular phylogenetic studies. For example, RAG1, a representative NPCL marker, has been successfully used to make phylogenetic inferences within all major osteichthyan groups. However, such markers with broad working rang...