The colonization of land by tetrapod ancestors is one of the major questions in the evolution of vertebrates. Despite intense molecular phylogenetic research on this problem during the last 15 years, there is, until now, no statistically supported answer to the question of whether coelacanths or lungfish are the closest living relatives of tetrapods. We determined DNA sequences of the nuclear-e...

Amorphic mutations in the recombination activating genes RAG1 and RAG2 have been reported to cause T- B- SCID, whereas hypomorphic mutations led to the expansion of a few autoimmune T cell clones responsible for the Omenn syndrome phenotype. We report here a novel clinical and immunological phenotype associated with recessive RAG1 hypomorphic mutations in 4 patients from 4 different families. T...

Lymphocytes represent a potentially important proinflammatory cell that localizes to atherosclerotic lesions. To determine whether they contribute to lesion development, atherosclerosis-prone (LDLR(-/-)) mice were crossed with lymphocyte-deficient (RAG1(-/-)) mice to generate double knockout progeny. After 8 weeks on a Western-type diet (WTD), lesion development was reduced by 54% in double kno...

Bacterial endosymbionts can drive evolutionary novelty by conferring adaptive benefits under adverse environmental conditions. Among aphid species there is growing evidence that symbionts influence tolerance to various forms of stress. However, the extent to which stress inflicted on the aphid host has cascading effects on symbiont community dynamics remains poorly understood. Here we simultane...

The RAG proteins initiate V(D)J recombination by mediating synapsis and cleavage of two different antigen receptor gene segments through interactions with their flanking recombination signal sequences (RSS). The protein-DNA complexes that support this process have mainly been studied using RAG-RSS complexes assembled using oligonucleotide substrates containing a single RSS that are paired in tr...

AIM To determine the effect of overexpression of fibrinogen-like protein 2 (FGL2) on regulatory T cell (Treg) and effector T (Teff) cell function on T cell-induced colitis in Rag1-/- mice. METHODS Treg and Teff cells from fgl2-/-, fgl2+/+, and fgl2Tg mice were purified by FACS. They were studied in vitro for immunosuppressive activity and cell proliferation and in vivo for their effects on th...

Type 2 diabetes (T2D) is associated with increased cancer risk and cancer-related mortality. Data herein show that we generated an immunodeficient hyperinsulinemic mouse by crossing the Rag1(-/-) mice, which have no mature B or T lymphocytes, with the MKR mouse model of T2D to generate the Rag1(-/-) (Rag/WT) and Rag1(-/-)/MKR(+/+) (Rag/MKR) mice. The female Rag/MKR mice are insulin resistant an...

A chronic demyelinating disease results from murine infection with the neurotropic strain JHM of mouse hepatitis virus (MHV-JHM). Demyelination is largely immune mediated. In this study, the individual roles of CD4 and CD8 T cells in MHV-induced demyelination were investigated using recombination-activating gene 1-/- (RAG1-/-) mice infected with an attenuated strain of MHV-JHM. These animals de...

Regulation of V-(D)-J recombinations that occur in antigen receptor encoding genes remains poorly understood. Recently, two genes, RAG1 and RAG2, that are able to activate rearrangement of synthetic recombination substrates were cloned in mouse and a human gene homologous to RAG1 was described. To define the differentiation stages corresponding to RAG1 and RAG2 RNA expression, we have studied a...