Rearrangement of RAG-1 recombinase gene in radiation-sensitive 'wasted' mice

摘要

The recent cloning and characterization of recombinase genes (RAG- 1/RAG-2) expressed in lymphoid and possibly central nervous system tissues prompted us to examine expression of these genes in DNA repair-deficient/immunodeficient wasted mice (wst). Our results revealed expression of RAG-1 mRNA was detected in spinal cord or brain from wst/wst mice or their normal littermates (wst/(sm bullet)mice). In thymus tissue, a small RAG-1 transcript was detected in wst/wst mice that was not evident in thymus from control mice. In wst/(lg bullet) mice, a two-fold increase in RAG-1 mRNA was evident in thymus tissue. RAG-2 mRNA could only be detected in thymus tissue from wst/(sm bullet) and not from wst;/wst or parental control BCF(sub 1) mice. Southern blots revealed a rearrangement/deletion within the RAG-1 gene of affected wasted mice, not evident in known strain-specific parental or littermate controls. These results support the idea that the RAG-1 gene may map at or near the locus for the wasted mutation. In addition, they suggest the importance of recombinase function in normal immune and central nervous system development as well as the potential contribution of this gene family to the normal repair of radiation-induced DNA damage.