• PMP22 is predominantly expressed in the compact myelin of the peripheral nervous system, and its levels require strict regulation. Gene duplication-induced mutations of PMP22 lead to CMT1A, which makes up 50 - 70% of all CMT cases.
• Gene editing strategy: The BAC containing the whole human PMP22 genome sequence was randomly inserted into mouse genome in B-Tg(hPMP22) mice.
• mRNA expression analysis: Mouse Pmp22 mRNA were detectable in wild-type C57BL/6 mice and hemizygote B-Tg(hPMP22), Human PMP22 mRNA was detectable only in hemizygote B-Tg(hPMP22) but not in wild-type mice.  
• In vivo efficacy: Human PMP22 targeted nucleic acid drugs (from client) was efficacious in B-Tg(hPMP22) mice.
• Application: This product is used for pharmacodynamics and safety evaluation of CMT1A.

Gene targeting strategy for B-Tg(hPMP22) mice. The BAC containing the whole human PMP22 genome sequence was randomly inserted into mouse genome in B-Tg(hPMP22) mice.

Strain specific analysis of PMP22 mRNA expression in wild-type C57BL/6 mice and B-Tg(hPMP22) mice by RT-PCR. Sciatic nerve RNA were isolated from wild-type C57BL/6 mice (+/+) and hemizygote B-Tg(hPMP22) (Tg/+), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human PMP22 primers. Mouse Pmp22 mRNA were detectable in wild-type C57BL/6 mice and hemizygote B-Tg(hPMP22). Human PMP22 mRNA was detectable only in hemizygote B-Tg(hPMP22) but not in wild-type mice.

The inhibitory efficiency of the nucleic acid drugs against human PMP22 in hemizygote B-Tg(hPMP22) mice. The human PMP22 targeted nucleic acid drugs (provide by client) and saline were administered to the B-Tg(hPMP22) mice individually on day 0. The mice were sacrificed on day 21, and the sciatic nerve tissue was collected to detect the expression level of human PMP22 mRNA by qPCR. The human PMP22 mRNA in the treatment groups (siRNA) were significantly reduced compared to the control groups (saline), demonstrating that B-Tg(hPMP22) mice provide a powerful preclinical model for in vivo evaluation of human PMP22 targeted nucleic acid drugs. Values are expressed as mean ± SEM.

Note: This experiment was performed by the client using B-Tg(hPMP22) mice. All the other materials were provided by the client.