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Post-translational modification of O-linked β-N-acetylglucosamine involves the addition of monosaccharide N-acetyl glucosamine (GlcNAc) to side chain hydroxyls of either serine or threonine residues of many cytoplasmic and nuclear proteins. O-GlcNAc (OGT) catalyzes the addition of GlcNAc, while removal of GlcNAc is catalyzed by O-GlcNAcase (OGA also know as NCOAT). Increased O-GlcNAc levels are associated with multiple conditions including diabetes, cataracts, proteosome inhibition, mammary development, and muscle atrophy.
Inducible TRE-GK-NCOAT transgenic mice express a short splice variant (GK-NCOAT) that replaces the corresponding Oga mouse sequence and is fused to an EGFP reporter under the control of the tetracycline responsive element (TRE, tetO) promoter. GK-NCOAT is a naturally occurring NCOAT splice variant cloned from the brain tissue of the Goto-Kakizaki (GK) rat. (NCOAT[GK]) interacts with OGT but lacks O-GlcNAcase activity. The resulting chimeric mouse-rat OGA minus exon 8 (2466 bp), has a non-functional catalytic site. When bred with a mouse harboring tissue specific expression of the tetracycline activator (tTA) or rtTA (reverse transactivator) protein, the generation of a dominant-negative form of NCOAT results in the suppression of native O-GlcNAcase and a net increase in O-GlcNAcylated proteins in that tissue regulated by tetracycline or its analog doxycycline (dox). Mice homozygous for the transgene are viable and fertile.
Huang P, Ho SR, Wang K, Roessler BC, Zhang F, Hu Y, Bowe DB, Kudlow JE, Paterson AJ. Muscle-specific overexpression of NCOATGK, splice variant of O-GlcNAcase, induces skeletal muscle atrophy. Am J Physiol Cell Physiol. 2011 Mar;300(3):C456-65. doi: 10.1152/ajpcell.00124.2010. Epub 2010 Dec 22. (Medline PMCID: 3063975)
Wang K, Ho SR, Mao W, Huang P, Zhang F, Schwiebert EM, Kudlow JE, Paterson AJ. Increased O-GlcNAc causes disrupted lens fiber cell differentiation and cataracts. Biochem Biophys Res Commun. 2009 Sep 11;387(1):70-6. doi: 10.1016/j.bbrc.2009.06.132. Epub 2009 Jul 3. (Medline PMCID: 2736685)
Cryo-recovered strains distributed by the MMRRC at JAX are shipped to the customer from the Pathogen & Opportunistic-Free Animal Room G200 - see https://www.jax.org/jax-mice-and-services/customer-support/customer-service/animal-health/health-status-reports.
Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.
The donor or their institution limits the distribution to non-profit institutions only.
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.
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.
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