ALPL Mouse
Description
Definition and Overview of ALPL Mouse Models
The term "ALPL Mouse" refers to murine models genetically engineered to study the role of the alkaline phosphatase, liver/bone/kidney (ALPL) gene, also known as tissue-nonspecific alkaline phosphatase (TNAP). These models include knockout (KO), heterozygous, and variant-bearing mice, designed to investigate ALPL’s function in bone mineralization, stem cell regulation, and metabolic diseases like hypophosphatasia (HPP).
Structure and Function of ALPL
ALPL is a glycosylated homodimer anchored to the cell membrane via a GPI-link. In mice, it spans residues Phe18-Gly503, with a C-terminal 6-His tag in recombinant forms . Key functions include:
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Hydrolysis of phosphate esters (e.g., inorganic pyrophosphate, pyridoxal 5′-phosphate), enabling mineralization of bones and teeth .
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Regulation of stem cell differentiation: Balances osteo-adipogenic lineage commitment in mesenchymal stem cells (MSCs) .
Table 1: Key Features of Recombinant Mouse ALPL
| Parameter | Value | Source |
|---|---|---|
| Sequence Domain | Phe18-Gly503 | |
| Tag | C-terminal 6-His | |
| Specific Activity | >46,000 pmol/min/µg (4-MUP substrate) | |
| Formulation | Tris/NaCl buffer (0.2 µm filtered) | |
| Purity | >95% (SDS-PAGE) |
3.1. Knockout (Alpl⁻/⁻) and Heterozygous (Alpl⁺/⁻) Mice
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Alpl⁻/⁻ mice:
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Alpl⁺/⁻ mice:
3.2. Conditional Knockout and Mutant Models
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Col1a1-Cre-driven Alpl KO:
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ENU-induced mutations:
4.1. Hypophosphatasia (HPP) Pathophysiology
ALPL deficiency in mice mirrors human HPP:
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Biochemical hallmarks: Low serum ALP activity, elevated urinary phosphoethanolamine (PEA) .
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Therapeutic insights: Metformin rescues MSC function in ALPL-deficient mice by modulating AMPKα/ATP pathways .
4.2. Stem Cell Regulation
Mechanisms in MSCs:
| Process | ALPL⁺/⁻ Phenotype | Wild-Type Comparison | Source |
|---|---|---|---|
| Osteogenesis | ↓ Runx2, ↓ OCN (osteogenic markers) | ↑ | |
| Adipogenesis | ↑ PPARγ (adipogenic marker) | ↓ | |
| Senescence | ↑ p16, ↑ SA-β-gal | ↓ |
5.1. Recombinant Proteins
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Catalog #2910-AP (R&D Systems):
5.2. Antibodies
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Anti-Mouse ALPL Antibody (AF2910):
Cross-Species Relevance and Clinical Implications
Product Specs
Product Science Overview
Alkaline phosphatase exists in multiple isoforms, each encoded by different genes and exhibiting tissue-specific expression. In humans, there are four distinct genes encoding alkaline phosphatases:
The liver/bone/kidney isozyme of alkaline phosphatase, encoded by the ALPL gene, is highly expressed in these tissues and plays a vital role in various biological processes:
Recombinant alkaline phosphatase is produced using genetic engineering techniques, where the gene encoding the enzyme is inserted into a host organism, such as bacteria or yeast, to produce the enzyme in large quantities. This recombinant form is used in research and clinical applications due to its high purity and consistency.
Recombinant alkaline phosphatase is widely used in various research and medical applications:
- Diagnostic Marker: Elevated levels of alkaline phosphatase in the blood can indicate liver disease, bone disorders, or other health conditions .
- Biochemical Research: Used to study enzyme kinetics, substrate specificity, and regulatory mechanisms.
- Therapeutic Use: Investigated for potential therapeutic applications in conditions such as hypophosphatasia, a rare genetic disorder affecting bone mineralization .
The activity of alkaline phosphatase is regulated by various factors, including:
- Phosphate Levels: High phosphate levels can inhibit the enzyme’s activity.
- Hormones: Hormones such as parathyroid hormone (PTH) and vitamin D can influence the expression and activity of alkaline phosphatase.
- Post-Translational Modifications: Glycosylation and other modifications can affect the enzyme’s stability and function .
