Though these mouse models are relatively close to human pathology, optimizing knockdown efficiency for therapeutic effectiveness without completely disrupting the gene is a therapeutic challenge for human CMT1A patients with three copies of the PMP22 gene, and excessive knockdown could cause pathologies similar to the PMP22 deletion (hereditary neuropathy with liability to pressure palsies (HNPP) that cause rare cases of hereditary neuropathy due to the loss of function21,22). This evidence concerns the gene PMP22 and Charcot-Marie-Tooth disease type 1A.