AID and RAG1 do not contribute to lymphomagenesis in Emu c-myc transgenic mice.
DNA breaks caused by recombination-activating gene 1 (RAG1) and activation-induced cytidine deaminase (AID) induce c-myc/immunoglobulin (Ig) heavy chain chromosomal translocations and thereby stimulate lymphomagenesis. However, constitutive expression of c-myc alone is not sufficient to induce lymphomas. Because RAG1 and AID activity occurs outside of Ig genes, we assessed whether these enzymes provide the secondary genetic lesions in Emu c-myc transgenic mice to promote lymphoma development. We found that the tumor incidence and tumor phenotype in Emu c-myc transgenic mice is similar in AID+/+, AID+/- and AID-/- backgrounds in both specific pathogen-free and conventional animal facilities, indicating that AID does not contribute to lymphoma development in Emu c-myc transgenic mice. To examine the role of RAG proteins in Emu c-myc mice, we examined Emu c-myc transgenic mice that harbor the Ig-HEL heavy- and light-chain transgenes, and thus have reduced RAG expression in B cells. We found that tumor incidence was not affected by these Ig transgenes. However, we found that RAG1-/- Emu c-myc mice exhibited accelerated tumor development compared to controls. This data combined with our finding that Emu c-myc mice lived longer in the conventional facility than in the specific pathogen-free facility suggest an immune-mediated activity that suppresses lymphoma development.
Nepal
R M
RM
Department of Immunology, University of Toronto, Medical Sciences Building, Toronto, Canada.
Zaheen
A
A
Basit
W
W
Li
L
L
Berger
S A
SA
Martin
A
A
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003564:Cytidine Deaminase / Q000235:genetics / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D015994:Incidence; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000401:mortality; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D016019:Survival Analysis; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D018398:Homeodomain Proteins; D007148:Immunoglobulin mu-Chains; D015514:Oncogene Proteins, Fusion; D016271:Proto-Oncogene Proteins c-myc; C064658:RAG-1 protein; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase