An ENU-induced mutation in the lymphotoxin alpha gene impairs organogenesis of lymphoid tissues in C57BL/6 mice.
The TNF family is critical for development of lymphoid organs and plays significant roles in regulation of innate and adoptive immune responses. Here, we describe a novel N-ethyl-N-nitrosourea (ENU)-induced mutant strain, HLB382, with a point mutation in the Lta gene, which encodes lymphotoxin (LT) alpha, a member of the TNF family. Mutant mice had no lymph nodes and no Peyer's patches. Microscopically, the spleens had disordered follicles and no germinal centers or discernible marginal zones (MZ). While the development of T cells and follicular B cells was normal, the numbers of NK and MZ B cells were significantly reduced. Interestingly, the numbers of peritoneal B1b cells were significantly increased. Genomic DNA sequences revealed a single base pair insertion in the coding region of Lta resulting in a frame shift and a premature stop codon. This new strain provides opportunities for understanding the full range of Lta gene function on a pure C57BL/6 background.
Wang
Hongsheng
H
Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5640 Fishers LN, TB1, Rm 1518, Rockville, MD 20852, USA. wanghongs@niaid.nih.gov
Feng
Jianxun
J
Qi
Chenfeng
C
Morse
Herbert C
HC
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology; D002874:Chromosome Mapping; D003713:Dendritic Cells / Q000276:immunology; D005038:Ethylnitrosourea / Q000633:toxicity; D006098:Granulocytes / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008198:Lymph Nodes / Q000002:abnormalities* / Q000166:cytology / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D038081:Organogenesis / Q000235:genetics*; D010537:Peritoneum / Q000276:immunology; D010581:Peyer's Patches / Q000002:abnormalities* / Q000166:cytology / Q000276:immunology; D017354:Point Mutation; D013601:T-Lymphocytes / Q000276:immunology
D008233:Lymphotoxin-alpha; D005038:Ethylnitrosourea