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Alzheimer's amyloid precursor protein mRNA without exon 15 is ubiquitously expressed except in the rat central
T Ohgami1, T Kitamoto, J Tateishi
1Department of Neuropathology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Abstract:
The expression of L-beta A4 amyloid precursor protein (L-APP) mRNA, which is a splicing product excluding exon 15 of the APP gene, was investigated in various tissues of adult rats by a polymerase chain reaction analysis of reverse-transcribed RNA (RT-PCR). L-APP mRNA was ubiquitously expressed in all the examined tissues including the liver, kidney, heart, skeletal muscle, spleen, thymus, adrenal, stomach, submandibular gland, testis and ovary, except for the central nervous system (CNS) tissues such as the brain and spinal cord. The DNA sequence analysis of the RT-PCR products from adult rat liver showed an L-APP cDNA form, in which exon 14 was spliced from exon 14 to exon 16, and exon 15 of the APP gene was excluded. In addition, regarding as the brain and liver, L-APP mRNA expression was examined during the development of the embryonic stage. In the brain, no L-APP mRNA expression was detected even in the embryonic stage, whereas L-APP mRNA expression of the liver was still found in the embryonic stage. These results suggest that the splicing event excluding exon 15, which is exactly adjacent to exon 16 and exon 17 encoding the beta A4 protein, would probably occur very rarely in the CNS and that the splicing of L-APP might already be regulated in the embryonic stage.
Insights
L-beta A4 amyloid precursor protein (L-APP) mRNA is widely expressed in rat tissues but absent in the central nervous system. This specific splicing event, excluding exon 15, appears regulated early in development.
Area of Science:
- Molecular Biology
- Neuroscience
- Genetics
Background:
- The amyloid precursor protein (APP) gene is central to understanding Alzheimer's disease pathology.
- Alternative splicing of APP mRNA generates various isoforms with distinct functions.
- L-APP mRNA, excluding exon 15, represents a specific splicing variant whose tissue distribution and developmental regulation are not fully understood.
Purpose of the Study:
- To investigate the expression pattern of L-APP mRNA across different adult rat tissues.
- To determine the developmental expression of L-APP mRNA in the brain and liver.
- To elucidate the potential role of exon 15 exclusion in APP processing and CNS function.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) was employed to detect L-APP mRNA.
- DNA sequencing was used to confirm the L-APP cDNA structure.
- Comparative analysis of L-APP mRNA expression in embryonic and adult tissues.
Main Results:
- L-APP mRNA was ubiquitously detected in all non-central nervous system (CNS) tissues examined, including liver, kidney, and heart.
- No L-APP mRNA expression was found in adult or embryonic CNS tissues (brain and spinal cord).
- Liver exhibited L-APP mRNA expression in both embryonic and adult stages, suggesting early developmental regulation.
Conclusions:
- The splicing event excluding exon 15 of the APP gene is rare in the CNS.
- L-APP mRNA expression is tightly regulated and appears to be established early in embryonic development.
- These findings suggest a tissue-specific function for L-APP and its potential role in non-CNS tissues.