Impact of Automated Genotyping and Increased Breeding Oversight on Overall Mouse Breeding Colony Productivity

Abstract

Mice have become increasingly popular as genetic tools, facilitated by the production of advanced genetically engineered mouse models (GEMMs). GEMMs often require in-house breeding and production by research groups, which can be quite complex depending on the design of the GEMM. Identification of methods to increase the efficiency of breeding practices offers opportunities to optimize and reduce the number of animals bred for research while maintaining similar research output. We investigated the use of commercial automated genotyping and centralized breeding management on overall breeding colony productivity in a colony of multiple GEMM lines. This study involved a three-group study design, where the first group continued their standard breeding practices (group A), the second utilized standard breeding practices but outsourced genotyping in place of inhouse genotyping (group B), and a third group outsourced genotyping and had assistance with routine breeding practices from the laboratory animal care team (group C). Compared to standard practice (group A), groups B and C produced more cages and mice over time, which appeared to be driven primarily by an increase in the number of breeding cages in each colony. Higher numbers of breeders correlated with an increased number of litters and generation of new cages. The increases in colony productivity measures were further enhanced in group C compared to group B. The overall cost associated with producing new animals was lowest in group B, followed by groups A and C. Although, by the end of the study, cost to produce new mice was comparable between all three groups. These data suggest that by optimizing breeding practices and management, fewer animals could be utilized to produce the same amount of progeny and reduce overall animal usage and production.

Keywords: 3Rs (replace; breeding; genetically engineered (GE) animals; genotyping; mouse model; reduce; refine).

FIGURE 1

Schematic figure representing the study groups A-C and overall study design.

FIGURE 2

Breeding management and automated genotyping impact overall colony size. (A) Total number of mice for each group over the time (Mixed effect linear regression, p = 0.0127, 2.66e-07 for Group B and C) (B) Total number of cages for each group over time (Mixed effect linear regression, p = 6.34e-07, Group C) (C) Correlation of number of mice vs. number of cages (Spearman correlation r = 0.924, 0.779, 0.744, p = 4.461 e −08, 1.392 e −0.4, 4.021 e −04 for Group A, B, C).

FIGURE 3

Increased breeding management and automated genotyping increased breeding efficiency. (A) Cage census for breeding (dark blue) and non-breeding (light blue) cages for Groups A-C. Line represents the total cage census. (B) Ratio of number of litters to total number of breeders for each group over time (Mixed effect linear regression, p = 0.00038, 0.0037 Group B, C) (C) Number of breeding cages compared to number of litters for Groups A-C (Spearman correlation r = 0.291, 0.622, 0.748 p = 0.335, 0.023, 0.0033) (D) Number of breeding cages compared to number of new barcodes for each group over time (Spearman correlation r = 0.051, 0.618, 0.786, p = 0.883, 0.0427, 0.0018)

FIGURE 4

Automated genotyping is associated with increased generation of new cages and breeding performance index. (A) Average cage census for the study colony from December through April in past years. (B) Active census days per barcode for all cages in Groups A-C (p = 1.69 e-06, Tukey post hoc test, p = 4.446 e −4, 1.0 e−6, A vs. B, A vs.C) (C) Percent change in average mouse age from baseline over time for Groups A-C (p = 4.99 e−06, 0.0617. Group (B, C) (D) Distribution of number of mice per cage for each of the groups (Mixed effect linear regression, p = 1.35 e−09, 1.92 e−10, Group B, C).

FIGURE 5

Breeding management and automated genotyping strategy impacts overall cost efficiency of mouse production. (A) Total cost for each day calculated consisting of total per diem costs per 2-week interval plus genotyping cost associated with new mouse production during that time frame (p = 0.00014) (B) Ratio of total costs to census new cage generated (new barcodes) over time for the three groups (p = 0.784,0.0135)