Backcrossing to an appropriate genetic background improves the birth rate of carbohydrate sulfotransferase 14 gene-deleted mice

摘要

Ehlers–Danlos syndromes (EDSs) are heterogeneous group of heritable connective tissue disorders characterized by joint and skin hyperextensibility as well as fragility of various organs. Recently, we described a new type of EDS, musculocontractual EDS (mcEDS- CHST14 ), caused by pathogenic variants of the carbohydrate sulfotransferase 14 ( CHST14 ) gene mutation. B6;129S5- Chst14 tm1Lex /Mmucd (B6;129- Chst14 KO) mice are expected to be an animal model of mcEDS- CHST14 . However, 90% of B6;129- Chst14 KO homozygous (B6;129- Chst14 ?/? ) mice show perinatal lethality. Therefore, improvement of the birth rate of Chst14 ?/? mice is needed to clarify the pathophysiology of mcEDS- CHST14 using this animal model. Some B6;129- Chst14 ?/? embryos had survived at embryonic day 18.5 in utero , suggesting that problems with delivery and/or childcare may cause perinatal lethality. However, in vitro fertilization and egg transfer did not improve the birth rate of the mice. A recent report showed that backcrossing to C57BL/6 strain induces perinatal death of all Chst14 ?/? mice, suggesting that genetic background influences the birthrate of these mice. In the present study, we performed backcrossing of B6;129- Chst14 KO mice to a BALB/c strain, an inbred strain that shows lower risks of litter loss than C57BL/6 strain. Upon backcrossing 1 to 12 times, the birth rate of Chst14 ?/? mice was improved with a birth rate of 6.12–18.64%. These results suggest that the genetic background influences the birth rate of Chst14 ?/? mice. BALB/c congenic Chst14 ?/? (BALB. Chst14 ?/? ) mice may facilitate investigation of mcEDS- CHST14 . Furthermore, backcrossing to an appropriate strain may contribute to optimizing animal experiments.