Post-translational modification of O-linked &beta;-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. &nbsp;

TRE-GK-NCOAT transgenic mice may be bred to generate Tet-Off/Tet-On mutant mice with conditional (inducible/reversible) expression of a short splice variant of (GK-NCOAT) of Oga (O-GlcNAcase or NCOAT) and a GFP reporter. The GK variant has non-functional catalytic site. The strain maybe useful for studying modification of O-linked &beta;-N-acetylglucosamine in diabetes (cataracts), mammary development, and muscle atrophy.

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