In this context, the Harlequin (Hq) mouse – a preclinical model of MD harboring a proviral insertion in Aifm1 causing an ∼80% decrease in AIF expression – has provided some mechanistic insight into the biological alterations leading to cerebellar degeneration (Klein et al., 2002; Vahsen et al., 2004; Bénit et al., 2008). This evidence concerns the gene AIFM1 and Menkes disease.