The murine Irs1 knockout model, generated by the spontaneous Irs1S57X mutation in homozygosity, exhibits high embryonic lethality, limiting studies of adult hematopoiesis

INTRODUCTION: mice and assessed fetal lethality in homozygous mice. METHODS: Hematological parameters were analyzed monthly in wild-type and heterozygous mice from 8 to 22 weeks of age. Successive intercrosses failed to yield homozygous knockouts. Fetal lethality was evaluated through timed matings of heterozygous mice, with genotyping performed at various gestational stages (E9.5, E12.5, E15.5 and E18.5). RESULTS: mice exhibited fetal or postnatal lethality as fetuses developed until gestational stage E18.5 but were either aborted or died shortly after birth. CONCLUSION: is associated with markedly reduced perinatal survival, precluding adult hematopoiesis studies. Future research should focus on fetal hematopoiesis.