It was also shown by our group that α2A/α2CARKO mice display severe pathological cardiac remodeling, activation of renin-angiotensin system and impaired calcium handling [24], [27], [28], [33], which are paralleled by a 30% mortality rate observed at the 7th month of age (Information S3), supporting the rationale of using α2A/α2CARKO mice as a model of severe HF. The gene discussed is REN; the disease is hydrops fetalis.