B6.Cg-Tg(PMP22)C3Fbas/2J

Stock number: 037871
Product name: C3-PMP low copy line
Strain synonyms: PMP22-C3 low copy line
Research areas: Neurobiology Research

Description

Stock No. 037871 is a C3-PMP22 low copy strain derived from Stock No. 030052 hemizygous pedigrees identified having ~1 copy of the C3-PMP22 YAC transgene. They express a wildtype human peripheral myelin protein 22 (PMP22) gene making these mice may be useful for studying Charcot-Marie-Tooth disease type 1A (CMT1A).
Please see Important Note for information regarding transgene copy number, as well as the Detailed Description section "February 2026 Quality Control Findings" for additional information on transgene copy number and phenotype.

Detailed description

Please see Important Note for information regarding transgene copy number, as well as the Detailed Description section "February 2026 Quality Control Findings" for additional information on transgene copy number and phenotype.

In an attempt to offer a strain with stable transgene low copy number, Stock No. 037871 was established in March 2024 from low copy (~1 transgene copy) hemizygous pedigrees identified within Stock No. 030052 (and thereafter Stock No. 030052 was maintained with high copy [~5 transgene copies] pedigrees). It should be noted that the Stock No. 037871 phenotype could vary from that originally described as having "3-4 copies" in its primary publication [Verhamme et al., 2011 J Neuropathol Exp Neurol 70:386]. We may modify the strain description if necessary as published results become available (e.g., see February 2026 Quality Control Findings below). Please also see Important Note for more information regarding transgene copy number.

Peripheral myelin protein 22 (PMP22) is a tetraspan glycoprotein contained in compact myelin of the peripheral nervous system. Duplication of PMP22 have been associated with the onset of Charcot-Marie-Tooth disease type 1A (CMT1A). This age-dependent demyelinating neuropathy is characterized by predominantly distal loss of strength and sensation that often develops in the first 2 decades of life.

C3-PMP22 YAC transgenic mice (also called C3-PMP) express a wildtype human peripheral myelin protein 22 (PMP22) gene. Please see Stock No. 030052 for description of the C3-PMP22 mice identified by quantitative real-time PCR to have three to four copies of the YAC in the donation laboratory's publication Verhamme et al., 2011.

The donating investigator for Stock No. 030052 reported that homozygous mice are viable but are more affected by the neuromuscular impairment than hemizygous animals. Males do not breed well. Line is maintained by breeding hemizygous females with wildtype males.

February 2026 Quality Control Findings by The Jackson Laboratory:
  In February 2026, additional quality control analyses were concluded by The Jackson Laboratory comparing Stock No. 030052 C3-PMP22 high copy (~5 transgene copies) hemizygous mice with Stock No. 037871 C3-PMP22 low copy (~1 transgene copy) hemizygous mice.
  This showed Stock No. 030052 hemizygotes (~5 transgene copies) expressed human PMP22 levels ~1.1x that of total endogenous (wildtype) mouse Pmp22. Furthermore, Stock No. 030052 hemizygous mice (~5 transgene copies) exhibit a strong, early onset CMT1A phenotype, characterized by electrophysiological impairment beginning at ~3 weeks of age [via compound muscle action potential and nerve conduction velocity assays], motor dysfunction by ~8 weeks of age [via rotarod, grip strength and wire hang assessments], and elevated serum neurofilament light (NfL) at ~32 weeks of age. This also confirmed that Stock No. 030052 hemizygous mice express human PMP22 levels sufficient to produce a detectable CMT1A-like phenotype within the examined timeframes.
  In contrast, Stock No. 037871 hemizygotes (~1 transgene copy) expressed human PMP22 levels only 0.3-0.4x that of total endogenous (wildtype) mouse Pmp22. Furthermore, Stock No. 037871 hemizygous mice were phenotypically indistinguishable from wildtype across those same electrophysiological, behavioral, molecular, and biomarker measures through 26-32 weeks of age. This suggests Stock No. 037871 hemizygous mice have an insufficient level of human PMP22 expression needed to trigger any significant spontaneous CMT1A neuropathy phenotype in the timeframes examined.

Development

A yeast artificial chromosome (YAC) library was used to obtain a 560 kb BAC (49G7, also called 49H7) containing the entire human peripheral myelin protein 22 (PMP22) gene. This YAC also contains gene encoded in the proximal part of a region duplicated in patients afflicted with Charcot-Marie-Tooth disease type 1A (CMT1A). This YAC was microinjected into fertilized (C57BL/6J × CBA/Ca) F1 oocytes. Founder PMP22 mice, termed C22, carrying 7 copies of the YAC on Chromosome 12 were established (Huxley et al., 1996 Hum Mol Genet 5:563) and bred to C57BL/6J inbred mice for at least 10 generations. As described in Verhamme et al., 2011 J Neuropathol Exp Neurol 70:386, some PMP22-C22 mice were observed with a milder phenotype and determined by quantitative real-time PCR to have a stable genotype with reduced human PMP22 copy number compared to PMP22-C22. The mice carrying three to four copies of the YAC were then maintained as a separate colony termed C3-PMP22 (please see Important Note for information regarding transgene copy number). The C3-PMP22 mice were further backcrossed for at least 10 generations to C57BL/6J mice by the donating lab (see SNP note below) and sent to The Jackson Laboratory in 2017. Upon arrival, it was bred to C57BL/6J (Stock No. 000664) at least one generation to establish Stock No. 030052. In 2024, a low copy (~1 transgene copy) pedigree was identified and those mice were used to establish Stock No. 037871.

A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the Stock No. 030052 males sent to The Jackson Laboratory in 2017. One of the 43 markers, on Chromosome 12, was found to be segregating with an unknown source - suggesting the transgene integration site is on Chr.12 (consistent with Huxley et al., 1996).

Allele

Symbol: Tg(PMP22)C3Fbas
Name: transgene insertion C3, Frank Baas
MGI accession ID: MGI:5817396
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: C3-PMP
Marker symbol: Tg(PMP22)C3Fbas
Marker name: transgene insertion C3, Frank Baas
Chromosome: UN
Strain of origin: (C57BL/6J x CBA/Ca)F1
Expressed genes: PMP22,peripheral myelin protein 22,human
Site of expression: Peripheral nervous system myelin.
Molecular note: A yeast artificial chromosome (YAC) library was used to obtain a 560 kb BAC (49G7, also called 49H7) containing the entire human peripheral myelin protein 22 (PMP22) gene. Line C3 is derived from founder line C22 and carries 3-4 copies of the YAC, resulting in a milder phenotype than the higer copy number C22 mice. Overexpression of PMP22 is associated with Charcot-Marie-Tooth disease type 1A (CMT1A).