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A novel mouse model expressing human forms for complement receptors CR1 and CR2
BACKGROUND: The complement cascade is increasingly implicated in development of a variety of diseases with strong immune contributions such as Alzheimer’s disease and Systemic Lupus Erythematosus. Mouse models have been used to determine function of central components of the complement cascade such...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487969/ https://www.ncbi.nlm.nih.gov/pubmed/32907542 http://dx.doi.org/10.1186/s12863-020-00893-9 |
Sumario: | BACKGROUND: The complement cascade is increasingly implicated in development of a variety of diseases with strong immune contributions such as Alzheimer’s disease and Systemic Lupus Erythematosus. Mouse models have been used to determine function of central components of the complement cascade such as C1q and C3. However, species differences in their gene structures mean that mice do not adequately replicate human complement regulators, including CR1 and CR2. Genetic variation in CR1 and CR2 have been implicated in modifying disease states but the mechanisms are not known. RESULTS: To decipher the roles of human CR1 and CR2 in health and disease, we engineered C57BL/6J (B6) mice to replace endogenous murine Cr2 with human complement receptors, CR1 and CR2 (B6.CR2CR1). CR1 has an array of allotypes in human populations and using traditional recombination methods (Flp-frt and Cre-loxP) two of the most common alleles (referred to here as CR1(long) and CR1(short)) can be replicated within this mouse model, along with a CR1 knockout allele (CR1(KO)). Transcriptional profiling of spleens and brains identified genes and pathways differentially expressed between mice homozygous for either CR1(long), CR1(short) or CR1(KO). Gene set enrichment analysis predicts hematopoietic cell number and cell infiltration are modulated by CR1(long), but not CR1(short) or CR1(KO). CONCLUSION: The B6.CR2CR1 mouse model provides a novel tool for determining the relationship between human-relevant CR1 alleles and disease. |
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