Murine model for Congenital Dyserythropoietic Anemia Type I

Congenital Dyserythropoietic Anemia type I (CDA-I) is an autosomal recessive disease characterized by anemia due to ineffective erythropoiesis and results primarily from mutations in CDAN1, which encodes CODANIN1. Research efforts to understand the CDA-I pathogenesis have been impeded by the embryonic lethality of germline Cdan1 deleted mice as well as mice deleted for Cdan1 in the erythroid compartment, using the constitutively active EpoR-Cre allele. To study the function of CODANIN1 in adult erythropoiesis, we generated mice with inducible erythroid-specific biallelic Cdan1 deletion using the Gata1-CreERT2 allele. Following tamoxifen administration to adult mice, Cdan1 is excised, resulting in features of CDA-I, including anemia, impaired erythroid differentiation, disturbances in erythroblast cell cycle progression, and the finding of 'spongy' heterochromatin in bone marrow erythroblasts. These findings confirm a critical role for CODANIN1 in effective adult erythropoiesis and demonstrate the successful generation of an inducible CDA-I mouse model, which serves as a valuable platform for testing novel therapies for this orphan disease.