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Pompe disease is an inherited disorder caused by a deficiency of alpha glucosidase, encoded by the GAA gene. Lysosomal glycogen accumulates in tissues, including muscles (most notably skeletal and cardiac) and the central nervous system resulting in cardiac and skeletal muscle myopathy. Enzyme replacement therapy (ERT) using recombinant human GAA is used to treat Pompe disease. ERT successfully clears lysosomal glycogen from the heart but is less effective in skeletal muscle due to autophagic debris. This mouse model of Pompe disease (MLCcre:Atg7F/F:GAA-/-) combines the GAA knockout allele with a muscle-specific cre recombinase (Myl1tm1(cre)Sjb, myosin, light polypeptide 1), and an Atg7 (autophagy related 7) allele with loxP sites flanking the cysteine active site. The presence of cre in the strain inactivates Atg7 in fast muscle fibers. MLCcre:Atg7F/F:GAA-/- mice develop the clinical signs of Pompe disease - muscle weakness, kyphosis, and muscle wasting (by 7-9 months of age). In addition, glycogen levels are reduced by 50-60% in fast muscle (but not cardiac or slow muscle), autophagy is suppressed in fast (gastrocnemius) muscle, and to a lesser degree in slow (soleus) muscle, and there are decreased numbers of lysosomes (and smaller in size) as compared to GAA-/- mice. Treatment of MLCcre:Atg7F/F:GAA-/- mice with ERT increases muscle glycogen to normal levels.
Raben N, Schreiner C, Baum R, Takikita S, Xu S, Xie T, Myerowitz R, Komatsu M, Van der Meulen JH, Nagaraju K, Ralston E, Plotz PH. Suppression of autophagy permits successful enzyme replacement therapy in a lysosomal storage disorder--murine Pompe disease. Autophagy. 2010 Nov;6(8):1078-89. doi: 10.4161/auto.6.8.13378. (Medline PMCID: 3039718)
Kohler L, Puertollano R, Raben N. Pompe Disease: From Basic Science to Therapy. Neurotherapeutics. 2018 Oct;15(4):928-942. doi: 10.1007/s13311-018-0655-y. (Medline PMCID: 6277280)
Lim JA, Sun B, Puertollano R, Raben N. Therapeutic Benefit of Autophagy Modulation in Pompe Disease. Mol Ther. 2018 Jul 5;26(7):1783-1796. doi: 10.1016/j.ymthe.2018.04.025. Epub 2018 May 3. (Medline PMCID: 6035739)
Jeong-A Lim, Lishu Li, and Nina Raben. Pompe disease: from pathophysiology to therapy and back again Frontiers of Neurology 2014; 7(309):ra9. doi: 10.1126Lim JA, Meena NK, Raben N. Pros and cons of different ways to address dysfunctional autophagy inPompe disease. Ann Transl Med. 2019 Jul;7(13):279. doi: 10.21037/atm.2019.03.51
Limited quantities of breeder mice (up to 2 males and 2 females or 4 mice) per investigator per month are available from a live colony, usually available to ship in under 12 weeks. Larger quantities may be available, please contact the distributing center directly at csmmrrc@jax.org for more details.
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.
A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Vidita Choudhry.
Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.
A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Vidita Choudhry
Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.
1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.
2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.
3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.
4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.