While heterozygous knockout mice possess a 50% reduction in ECHS1 expression, they develop normally with only mild lipid accumulation and a cardiomyopathy phenotype.25,26 To establish a model of disease, CRISPR/Cas9 was used to generate a knock-in (KI) mouse line that contains a disease-associated variant (c.98T>C; p.F33S) (Fig. 1).4 A knock-out (KO) line was also generated that possesses a frameshift mutation in exon 2 that results in an early stop codon. The gene discussed is ECHS1; the disease is cardiomyopathy.