MFN2R94Q:MFN1 transgenic mice contain a murine prion protein (Prnp) promoter driving expression of a flag-tagged wildtype human mitofusin 1 (MFN1) gene in the nervous system. They also contain a murine thymus cell antigen 1, theta (Thy1; Thy1.2) promoter driving expression of a flag-tagged human mitofusin 2 (MFN2) gene integrated on the Y chromosome. The MFN2 gene contains the dominant point mutation, R94Q. Mutations of this residue and neighboring residues in the GTPase domain have been associated with the onset of Charcot-Marie-Tooth disease type 2A (CMT2A) across numerous ethnic backgrounds with a consistently severe early-onset phenotype that, in addition to peripheral neuropathy, may include optic atrophy, spasticity, developmental delay, and brain white matter abnormalities. MFN1 may play a compensatory role in the onset of CMT2 driven by mutations or decreases in MFN2 expression. Stock No. 033391 is the double transgenic MFN2R94Q:MFN1 mouse line. Overexpression of MFN1 in the nervous system rescues the stunted growth and reduced survival seen in MFN2R94Q mice (details below). MFN2R94Q:MFN1 mice appear phenotypically normal with a normal gate, and do not exhibit clasping even at advanced ages. They also have marked improvement in rearing activity in open field testing, rotarod fall latency, and grip strength compared to MFN2R94Q mice. Mice carrying the Prp-MFN1 transgene alone are viable and fertile as homozygotes. They are indistinguishable from non-transgenic littermates. Mice carrying the MFN2R94Q transgene alone have stunted growth, and die prematurely from failure to thrive (25% died by 15 months of age). They have early onset of severe sensorimotor deficits. By 3-months of age, MFN2R94Q mice exhibit a wobbling gait defect and occasionally dragged their hindlimbs. By 10 months, MFN2R94Q mice have severe uncoordinated movements, and hindlimb paw clasping. They display vision loss, altered mitochondrial dynamics, and widespread axonal degeneration. [<a href="https://pubmed.ncbi.nlm.nih.gov/30882371">Zhou et al. 2019 J Clin Invest. 130:1756</a>] To help mitigate the phenotype severity of mice carrying the MFN2R94Q transgene alone, the donating investigator reports giving moist rodent chow every day post-wean and bacon softies (Bio-Serv, Catalog #F3580-1) every other day. Furthermore, these animals may develop eye secretions which can be treated with antibiotic ophthalmic ointment. They may also develop malocclusions that need trimming once a week. The Jackson Laboratory has observed the phenotype of mice carrying the MFN2R94Q transgene alone is more extreme with an earlier lethality than originally published. Our research animal facility reports providing DietGel76A to post-wean MFN2R94Q transgenic animals allows them to maintain hydration/nutritional status better than with water bottles and standard food pellets. This appears to greatly diminish the early lethality observed in the absence of dietary supplementation. In the absence of dietary supplement, MFN2R94Q mice do not reliably survive to wean, dying too early for shipment. Therefore, the more viable double transgenic MFN2R94Q:MFN1 mouse line (Stock No. 033391) is available for distribution.

MFN2R94Q:MFN1 mice express flag-tagged wildtype human prion protein (Prnp) promoter driving expression of a flag-tagged wildtype human mitofusin 1 (MFN1) gene in the nervous system. They also express a flag-tagged human mitofusin 2 (MFN2), containing an R94Q mutation, under direction of the murine Thy1 promoter. These mice may be useful when studying Charcot-Marie-Tooth Neuropathy Type 2 (CMT2).

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Our minimum guarantee for cryorecovery orders is 2 carriers. To ensure that your colony can be rapidly expanded upon arrival, additional carriers may be added to your order.

C57BL/6J-Tg(Prnp-MFN1)1Balo Tg(Thy1-MFN2*R94Q)44Balo/J