Refining the Sox10^Dom/+ mouse model: A new breeding strategy with relevance to Hirschsprung disease genetics

Abstract

Background: The traditional Sox10^Dom/+ mouse breeding strategy is costly and time-consuming, so this study aims to optimize the breeding method and improve the scientific research efficiency.

Methods: We select the offspring from mating B6C3Fe Sox10^Dom/+ male mice with C57BL/6J female mice, and name the progeny B6C3Fe-g. Further, conduct separate self-breeding for both the B6C3Fe and B6C3Fe-g strains, adhering to the principle of pairing mutants with non-mutants. By comparing the number of offspring, survival rates, and the phenotype of aganglionosis in the colon, a comprehensive evaluation of their breeding capacity and phenotypic stability is conducted.

Results: Sanger sequencing results show that the mutation sites of B6C3Fe and B6C3Fe-g mice are consistent. After fluorescent staining of intestinal nerves, it was found that the heterozygous mice of the two strains had neuronal deletion in the distal colon, and this pathological phenotype was consistent with the pathological features of the diseased colon of Hirschsprung disease (HSCR). However, compared with the B6C3Fe strain, the B6C3Fe-g strain has a higher number of offspring and greater survival rates.

Conclusions: The breeding strategy of the B6C3Fe-g strain ensures genetic and phenotypic stability, while improving reproductive efficiency, and is an ideal scheme for breeding Sox10^Dom/+ mice.

Keywords

B6C3Fe6 / B6C3Fe-g / Hirschsprung disease / Sox10

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2025 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.