Genetic analysis of low lambda 1 chain production in mice

Area of Science:

• Immunology
• Genetics
• Laboratory Animal Science

Background:

• Commonly used laboratory mouse strains (CF-1, CD-1, CFW) from Charles River Laboratories were investigated.
• Previous studies identified low or undetectable serum immunoglobulins (Ig) bearing lambda 1 light chains in some mouse populations.

Purpose of the Study:

• To investigate the prevalence and genetic basis of low lambda 1 Ig production in specific laboratory mouse strains.
• To compare the genetic defect in laboratory mice with lambda 1 Ig deficiency to that of SJL mice.
• To survey lambda 1 Ig production in wild mouse populations and explore potential regulatory mechanisms.

Main Methods:

• Serum samples from CF-1, CD-1, and CFW mice were analyzed for lambda 1 Ig levels.
• Mice were tested for lambda 1-specific anti-NP responses.
• Genomic DNA was analyzed for polymorphisms at the lambda 1 locus.
• Wild mice from diverse geographic locations were surveyed for lambda 1 Ig production.

Main Results:

• A strong correlation was observed between low serum lambda 1 Ig levels, reduced anti-NP responses, and specific genomic polymorphisms.
• Nearly all CFW mice, over 70% of CD-1 mice, and no CF-1 mice showed low lambda 1 Ig production.
• The genetic defect in CFW, CD-1, and SJL mice appears similar or identical, suggesting a common ancestor.
• Low lambda 1 Ig production was frequently observed in wild mice globally, but the defect seems distinct from laboratory strains.

Conclusions:

• Laboratory mouse strains CFW and CD-1 possess a genetic defect affecting lambda 1 Ig production, similar to SJL mice.
• The lambda 1 locus in CD-1, CFW, and SJL mice likely originated from a common ancestor.
• Wild mice exhibit diverse mechanisms regulating lambda 1 Ig production, with defects differing from those in common laboratory strains.