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Identification of a new form of AQP4 mRNA that is developmentally expressed in mouse brain
S Zelenin1, E Gunnarson, T Alikina
1Department of Woman and Child Health, Karolinska Institutet, Astrid Lindgren Children's Hospital, Stockholm, Sweden.
Abstract:
The water channel aquaporin 4 (AQP4) is abundantly expressed in the brain, and also in lung and kidney. Previous studies have suggested that there are at least two AQP4 mRNA. The two mRNA encode for two AQP4 proteins that differ with regard to the length of the N-terminal: AQP4.M1 and AQP4.M23. Here we report, by use of reverse transcriptase PCR and comparison of genomic and cDNA structures, the presence of a third form of mouse AQP4 mRNA. The upstream sequence of this form of mRNA originates from an additional exon, interspaced between exon 0 and exon 1, and an alternatively spliced form of exon 1. Analysis of nucleotide sequence suggests that this new form of AQP4 mRNA also encodes for the AQP4.M23 protein. The two forms of AQP4 mRNA that presumably both encode for M23 have a tissue- and age-specific expression. The new AQP4 mRNA was predominantly expressed in brain. The expression was approximately twofold higher in the adult brain than in the infant brain. In contrast, the expression levels of the new mRNA were low in both infant and adult lung and kidney. The previously described mRNA encoding for AQP4.M23 was predominantly expressed in lung and kidney. In lung, the expression of this form was higher in infancy than in adulthood. In conclusion, we have identified a new form of AQP4 mRNA that is predominantly expressed in the brain and that is developmentally regulated.
Insights
Researchers discovered a new form of aquaporin 4 (AQP4) mRNA predominantly in the brain. This AQP4 mRNA form shows developmental regulation, with higher expression in adult brains compared to infant brains.
Area of Science:
- Molecular Biology
- Neuroscience
- Physiology
Background:
- Aquaporin 4 (AQP4) is a key water channel protein found in the brain, lungs, and kidneys.
- Existing research identifies two AQP4 mRNA forms, encoding AQP4.M1 and AQP4.M23 proteins differing in N-terminal length.
Purpose of the Study:
- To investigate the existence and characteristics of additional AQP4 mRNA forms in mice.
- To determine the tissue- and age-specific expression patterns of newly identified AQP4 mRNA.
Main Methods:
- Reverse transcriptase PCR (RT-PCR) was employed to detect and analyze AQP4 mRNA.
- Genomic and cDNA structures were compared to identify novel exons and alternative splicing events.
- Nucleotide sequence analysis was performed to predict the protein product of the new mRNA form.
Main Results:
- A third form of mouse AQP4 mRNA was identified, originating from an additional exon and an alternatively spliced exon 1.
- This new AQP4 mRNA form is predicted to encode the AQP4.M23 protein.
- The new AQP4 mRNA exhibited predominant expression in the brain, with higher levels in adults than infants.
- Previously described AQP4 mRNA (encoding M23) showed higher expression in infant lung and was predominant in adult lung and kidney.
Conclusions:
- A novel AQP4 mRNA variant, predominantly expressed in the brain, has been discovered.
- This brain-specific AQP4 mRNA form is developmentally regulated, with increased expression in adulthood.
- Differential expression patterns of AQP4 mRNA forms suggest distinct roles in various tissues and developmental stages.