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The bm12 Inducible Model of Systemic Lupus Erythematosus (SLE) in C57BL/6 Mice
Published on: November 1, 2015
Mouse lymphomas caused by an intron-splicing donor site deletion of the FasL gene
Cheng-Chun Wang1, Qi Zeng, Le-Ann Hwang
1Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore.
Abstract:
A spontaneous lymphoma was detected in mice, which was caused by a recessive autosomal mutation. The genetic basis was revealed to be a 5-bp deletion at the splicing donor site of the first intron of the FasL gene, resulting in aberrant transcripts coding for non-functional proteins. This mutation of the FasL gene caused development of lymphoma in all four mouse genetic backgrounds tested and the lymphoma was characterized by an expansion of leucocytes that were TCR+CD3+B220+CD19-CD4-CD8-. Accordingly, severe splenomegaly developed in the mutant mice. Interestingly, thymic hyperplasia was observed in mutant mice at later stages. These results underscore the functional importance of the splicing donor site in the function of the FasL gene and provide an independent evidence for a role of FasL in normal development of lymophocytes. The mutant mice offer another genetically defined mouse model for further studies of the role and mechanism of action of FasL.
Insights
A mutation in the FasL gene causes lymphoma in mice by creating non-functional proteins. This study highlights the FasL gene's importance in lymphocyte development and offers a new mouse model for research.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- The Fas Ligand (FasL) pathway is crucial for immune system regulation.
- Mutations in genes involved in lymphocyte development can lead to lymphoproliferative disorders.
Purpose of the Study:
- To investigate the genetic basis of a spontaneous lymphoma observed in mice.
- To elucidate the role of the FasL gene in lymphocyte development and lymphoma pathogenesis.
Main Methods:
- Genetic analysis to identify the causative mutation.
- Transcriptional analysis to assess FasL gene function.
- Phenotypic characterization of lymphoma in mutant mice, including flow cytometry and organ examination.
Main Results:
- A 5-bp deletion in the FasL gene's splicing donor site was identified as the cause of lymphoma.
- Aberrant FasL transcripts led to non-functional proteins, irrespective of mouse genetic background.
- Mutant mice exhibited lymphoma characterized by specific leukocyte expansion (TCR+CD3+B220+CD19-CD4-CD8-), splenomegaly, and thymic hyperplasia.
Conclusions:
- The splicing donor site of the FasL gene is critical for its proper function.
- FasL plays a significant role in normal lymphocyte development.
- The identified mutant mice provide a valuable model for studying FasL function and related diseases.
