High-Throughput and Cost-Effective Genome-wide Microsatellite Genotyping of Two Novel Cystic Fibrosis Mutant Mouse Strains

Whole-genome scan experiments have been used extensively for the characterization of the classical laboratory inbred strains of mice generating panels of polymorphic and equally spaced microsatellite markers. In this report we describe the implementation of informative microsatellite markers in the genetic characterization of two novel inbred cystic fibrosis mutant strains, CF/1-Cftr^{TgH(neoim)1Hgu} and CF/3-Cftr^{TgH(neoim)1Hgu}, with a straightforward, time-efficient, and cost-effective genotyping procedure utilizing direct blotting electrophoresis. A whole-genome scan experiment was undertaken by selecting a panel of 105 microsatellite markers on the basis of spacing and polymorphism in the strains C57BL/6J, DBA/2J, and BALB/c, which were further used for the generation of congenic Cftr^{TgH(neoim)1Hgu} mutant animals. The genome-wide strain distribution of microsatellite alleles between the two inbred cystic fibrosis strains differed significantly from the three classical inbred strains. Moreover, using the Wagner parsimony method, we were able to generate a tree whereby the relatedness of the two novel inbred strains to the three classic laboratory inbred strains was determined. For C57BL/6J, DBA/2J, and BALB/c the results of the parsimony analysis were in agreement with the previously documented history of the inbred strains, whereas both cystic fibrosis inbred strains were placed as the most deeply divergent strains.