Recombinant Mouse N-acetylglucosamine-1-phosphotransferase subunits alpha/beta (Gnptab)
Description
General Information
The Gnptab gene provides the necessary instructions for creating the alpha and beta subunits of GlcNAc-1-phosphotransferase, an enzyme . This enzyme comprises two alpha, two beta, and two gamma subunits, with the gamma subunit originating from a separate gene known as GNPTG . GlcNAc-1-phosphotransferase is crucial in preparing newly synthesized enzymes for transportation to lysosomes, which are cell compartments that employ hydrolases to break down large molecules .
GlcNAc-1-phosphotransferase facilitates the production of mannose-6-phosphate (M6P), acting as a tag that directs hydrolases to the lysosome . It transfers a GlcNAc-1-phosphate molecule to a newly produced hydrolase .
Function and Importance
Gnptab is essential for the correct functioning of GlcNAc-1-phosphotransferase, which plays a vital role in lysosomal enzyme targeting . Mice lacking GlcNAc-1-phosphotransferase activity exhibit symptoms similar to those observed in humans with mucolipidosis types II and III . These symptoms include elevated plasma levels of lysosomal acid hydrolases due to the missing mannose 6-phosphate targeting signal .
Impact of Mutations
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Elevated Plasma Levels of Acid Hydrolases: Missense mutations in Gnptab can result in increased plasma activity levels of lysosomal acid hydrolases in mice . For example, GnptabSer321Gly mice displayed a 1.26- to 3.3-fold increase in the plasma activity level of β-hexosaminidase, α-mannosidase, and β-mannosidase .
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White Matter Deficits: Studies using diffusion tensor imaging (DTI) have revealed white matter deficits in Gnptab Ser321Gly mice . Specifically, there was a significantly reduced local volume in the genu of the corpus callosum (CC) in these mice .
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Increased Interbout Pause Durations: Gfap-specific Gnptab knockout mice showed significantly increased interbout pause durations . This was observed in conditional heterozygote knockouts (cHET) .
Research Findings
Research has focused on understanding the effects of GNPTAB mutations on various functions in mice. Some key findings include:
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Vocalization Phenotypes: GnptabAla455Ser mice vocalizations showed slight phenotypic differences, particularly when using different syllable cutoff values .
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Conditional Knockout Mice: Conditional knockout mice carrying the loxP sequence in the flanking regions of exon 2 of Gnptab were created to study astrocyte-specific knockout effects .
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Gnptab as a Host Factor: GNPTAB has been identified as a host factor for Ebola virus (EBOV) infection .
Data Tables
Table 1: Plasma Levels of Acid Hydrolases in Gnptab Ser321Gly Mice
| Acid Hydrolase | Wild-Type Mice | GnptabSer321Gly Mice | Fold Increase |
|---|---|---|---|
| β-Hexosaminidase | X | Y | 1.26-3.3 |
| α-Mannosidase | X | Y | 1.26-3.3 |
| β-Mannosidase | X | Y | 1.26-3.3 |
| β-Galactosidase | X | Y | NS |
| β-Glucuronidase | X | Y | NS |
Note: NS = No significant difference. Actual values (X, Y) not available in the original paper, but fold increase is reported .
Table 2: DTI Analysis of White Matter in Gnptab Ser321Gly Mice
| Brain Region | Wild-Type Mice (Mean ± SEM) | Mut/Mut Mice (Mean ± SEM) | P-Value |
|---|---|---|---|
| Genu of CC (LogJ) | -0.017 ± 0.011 | -0.16 ± 0.012 | 0.025 |
| Anterior Commissure | X | Y | 0.26 |
| Splenium | X | Y | 0.67 |
| Hippocampus | X | Y | 0.97 |
Note: Actual LogJ values (X, Y) not available for all regions in the original paper .
Product Specs
Note: We will prioritize shipping the format currently in stock. If you have specific format requirements, please indicate them during order placement.
Note: All proteins are shipped with standard blue ice packs. Dry ice shipping requires advance notification and incurs additional charges.
The tag type will be determined during production. If you require a specific tag, please inform us, and we will prioritize its development.
Target Background
This protein catalyzes the formation of mannose 6-phosphate (M6P) markers on high-mannose type oligosaccharides within the Golgi apparatus. M6P residues are crucial for binding to mannose 6-phosphate receptors (MPRs), which mediate the vesicular transport of lysosomal enzymes to the endosomal/prelysosomal compartment.
- A novel mouse model of MLII homozygous for a patient mutation in the GNPTAB gene. PMID: 25107912
- The DMAP interaction domain of the alpha subunit plays a role in the selective recognition of acid hydrolase substrates, explaining impaired acid hydrolase phosphorylation in mucolipidosis II patients. PMID: 23733939
- Retinal degeneration and storage disease phenotype in most exocrine glands observed in Gnptab null mice. PMID: 19261645
- Vacuolization in mucolipidosis type II mouse exocrine gland cells (GlcNAc-1-phosphotransferase-deficient mice) indicates the accumulation of autolysosomes. PMID: 21325625
