Mouse strains with typical mammalian levels of complement activity.

Area of Science:

• Immunology
• Mammalian Genetics
• Biomedical Research Models

Background:

• Standard laboratory mouse strains possess significantly lower serum complement levels than humans and other mammals.
• This deficiency limits the utility of conventional mice as experimental models in various biological and medical studies.
• Identifying mouse strains with higher complement activity is crucial for advancing research.

Purpose of the Study:

• To screen a diverse collection of mouse and rat strains for elevated serum complement levels.
• To identify and characterize laboratory animals with complement activity suitable for broader biomedical applications.
• To investigate the underlying genetic basis for high complement activity in selected mouse strains.

Main Methods:

• Serum complement activity was quantified in 43 mouse strains and 11 rat strains using erythrocyte and human tumor cell targets.
• Complement component levels (C1-C9) were assayed in high-complement BUB mice compared to standard BDF1 mice.
• Classical complement pathway activation was confirmed as the mechanism for target cell lysis.

Main Results:

• Eight mouse strains exhibited total complement activity comparable to other mammalian species.
• These high-complement mouse sera effectively lysed tumor cells, similar to human and rat sera, via the classical pathway.
• Elevated levels of complement components C3, C5, C6, and C7 were identified as the primary drivers of increased complement activity in BUB mice.

Conclusions:

• Several mouse strains possess high complement levels, significantly enhancing their value as experimental models.
• These 'high-complement' mouse strains, including newly identified ones and older strains like BUB/BnJ, DA/HuSn, and RIIIS/J, offer improved utility.
• The identified high-complement mouse strains and their derivatives hold promise for diverse biomedical research applications.