Pen-2 overexpression induces Aβ-42 production, memory defect, motor activity enhancement and feeding behavior dysfunction in NSE/Pen-2 transgenic mice.

Abstract

Pen-2 is a key regulator of the γ-secretase complex, which is involved in the production of the amyloid β (Aβ)-42 peptides, which ultimately lead to Alzheimer's disease (AD). While Pen-2 has been studied in vitro, Pen-2 function in vivo in the brains of transgenic (Tg) mice overexpressing human Pen-2 (hPen-2) protein has not been studied. This study aimed to determine whether Pen-2 overexpression could regulate the AD-like phenotypes in Tg mice. NSE/hPen-2 Tg mice were produced by the microinjection of the NSE/hPen-2 gene into the pronucleus of fertilized eggs. The expression of the hPen-2 gene under the control of the NSE promoter was successfully detected only in the brain and kidney tissue of NSE/hPen-2 Tg mice. Also, 12-month-old NSE/hPen-2 Tg mice displayed behavioral dysfunction in the water maze test, motor activity and feeding behavior dysfunction in food intake/water intake/motor activity monitoring system. In addition, tissue samples displayed dense staining with antibody to the Aβ-42 peptide. Furthermore, NSE/hPen-2 Tg mice exhibiting feeding behavior dysfunction were significantly more apt to display symptoms related to diabetes and obesity. These results suggest that Pen-2 overexpression in NSE/hPen-2 Tg mice may induce all the AD-like phenotypes, including behavioral deficits, motor activity and feeding behavior dysfunction, Aβ-42 peptide deposition and chronic disease induction.

• Authors: So Hee Nam, Su Jin Seo, Jun Seo Goo, Jee Eun Kim, Sun Il Choi, Hae Ryun Lee, In Sik Hwang, Seung Wan Jee, Su Hae Lee, Chang Jun Bae, Jung Youn Park, Hye Sung Kim, Sun Bo Shim, Dae Youn Hwang
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 28 Issue 6 Pg. 961-71 (Dec 2011) ISSN: 1791-244X [Electronic] Greece
• PMID: 21822534 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Membrane Proteins
• PSENEN protein, human
• Peptide Fragments
• amyloid beta-protein (1-42)
• Amyloid Precursor Protein Secretases

Topics

• Alzheimer Disease (genetics, metabolism, physiopathology)
• Amyloid Precursor Protein Secretases (genetics, metabolism)
• Amyloid beta-Peptides (biosynthesis, genetics)
• Animals
• Brain (metabolism, physiopathology)
• Disease Models, Animal
• Enzyme Activation (genetics)
• Feeding Behavior
• Female
• Gene Expression
• Humans
• Male
• Maze Learning (physiology)
• Membrane Proteins (genetics, metabolism)
• Memory
• Mice
• Mice, Transgenic
• Motor Activity (genetics)
• Neuroblastoma (genetics, metabolism, pathology)
• Peptide Fragments (biosynthesis, genetics)
• Plasmids (genetics)
• Transfection
• Tumor Cells, Cultured