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Updated: Jul 11, 2026
08:42
Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
Published on: July 3, 2020
A novel phosphatase upregulated in Akp3 knockout mice
Sonoko Narisawa1, Marc F Hoylaerts, Kutbuddin S Doctor
1Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
American Journal of Physiology. Gastrointestinal and Liver Physiology
|September 29, 2007
Summary
A novel gene, Akp6, compensates for the absence of intestinal alkaline phosphatase (IAP) in Akp3(-/-) mice, maintaining gut AP activity. This gIAP isozyme likely plays a role in fatty acid absorption, particularly in high-fat diets.
Area of Science:
- Biochemistry
- Genetics
- Molecular Biology
Background:
- Intestinal alkaline phosphatase (IAP) plays a role in nutrient absorption.
- The Akp3 gene encodes duodenum-specific IAP (dIAP).
- Akp3(-/-) mice lack dIAP but retain gut AP activity.
Purpose of the Study:
- To investigate the source of residual AP activity in Akp3(-/-) mice.
- To characterize the novel IAP isozyme responsible for this activity.
- To explore the functional implications of this novel isozyme.
Main Methods:
- Western and Northern blot analyses to detect gene expression.
- Enzymatic assays to determine kinetic properties (kcat, Km).
- Phylogenetic and developmental expression analysis.
Main Results:
- A novel murine Akp6 gene encodes a globally expressed IAP isozyme (gIAP).
- gIAP exhibits reduced catalytic efficiency (4-fold lower kcat/Km) compared to dIAP, attributed to an R317Q substitution.
- Akp6 is expressed from birth throughout the gut and upregulated in Akp3(-/-) mice, particularly in the jejunum and ileum.
- Akp3 expression is postnatal and duodenum-specific, while Akp6 and Akp5 are expressed early and globally.
Conclusions:
- Akp6-encoded gIAP compensates for Akp3-encoded dIAP in the mouse intestine.
- gIAP's properties and upregulation suggest a role in lipid metabolism, potentially mediating accelerated fatty acid intake in Akp3(-/-) mice on high-fat diets.
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