Functional deficiency in IL-7 caused by an N-ethyl-N-nitrosourea-induced point mutation.
N-ethyl-N-nitrosourea (ENU)-induced mutagenesis provides a powerful approach for identifying genes involved in immune regulation and diseases. Here we describe a new mutant strain, HLB368, with hereditary leukopenia. At necropsy, the mutant mice had very small thymuses and spleens. All but the inguinal nodes were absent and there were no Peyer's patches. By flow cytometry, the ratios of T-cell subsets were normal, but B-cell development was blocked at the pre-pro-B-cell stage. The development of B1 and marginal zone B cells was relatively normal. The mutation was mapped to chromosome 3 between D3Mit221 and D3Mit224, a region that contains the Il7 gene. cDNA and genomic DNA sequences of Il7 revealed a T-to-C missense transition resulting in a change of Leu to Pro within the leader peptide that would be predicted to inhibit secretion. In keeping with this concept, we found that in vitro treatment of B-cell progenitors from mutant mice with IL-7 induced them to differentiate into pre-BII cells. Phenotypic comparisons of HLB368 with genetically targeted Il7 null mice showed many similarities along with a few differences, indicating that this ENU-induced mutant carries a novel allele. This new strain thus provides a new model for studying the functions of IL-7 on a pure C57BL/6 background.
Feng
Jianxun
J
Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.
Wang
Hongsheng
H
Morse
Herbert C
HC
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002874:Chromosome Mapping; D005038:Ethylnitrosourea / Q000494:pharmacology*; D005434:Flow Cytometry; D015851:Interleukin-7 / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008221:Lymphoid Tissue / Q000002:abnormalities / Q000187:drug effects; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016296:Mutagenesis; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects
D015851:Interleukin-7; D005038:Ethylnitrosourea