Although strategies have been developed to increase disease severity in mouse models, such as the deletion of additional genes like utrophin (Utrn) (Deconinck et al., 1998) (Fig. 1) or cytidine monophosphate-N-acetylneuraminic acid hydroxylase (Cmah) (Chandrasekharan et al., 2010), larger animal models, i.e. the DMD rat (Szabó et al., 2021), dog (Hakim et al., 2021) and pig (Stirm et al., 2021), seem to better recapitulate these aspects of human disease (McGreevy et al., 2015). The gene discussed is UTRN; the disease is Duchenne muscular dystrophy.