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The pulmonary hypertensive fawn-hooded rat has a normal serotonin transporter coding sequence
A M Gonzalez1, A P Smith, C J Emery
1Respiratory Medicine, Division of Clinical Science, University of Sheffield Medical School, Sheffield, United Kingdom.
American Journal of Respiratory Cell and Molecular Biology
|August 12, 1998
Summary
The fawn-hooded rat (FHR) shows impaired serotonin storage, but its serotonin transporter gene sequence is identical to Wistar rats. This suggests the genetic cause of altered serotonin storage in FHR is not due to this gene.
Area of Science:
- Genetics
- Pharmacology
- Cardiovascular Science
Background:
- The fawn-hooded rat (FHR) exhibits inherited platelet storage-pool deficiency, impaired serotonin storage, and susceptibility to hypertension.
- FHR serves as a valuable genetic model for studying human systemic and pulmonary hypertension.
Purpose of the Study:
- To investigate the coding sequence of the serotonin transporter gene in Wistar and FHR strains.
- To determine if genetic differences in the serotonin transporter account for altered serotonin storage in FHR.
Main Methods:
- Comparison of the serotonin transporter gene coding sequence between Wistar and FHR rats.
- Analysis of platelet function, including serotonin uptake and release, using radiolabeled serotonin.
- Comparison of predicted amino acid sequences from platelet and lung samples with published brown rat sequences.
Main Results:
- Significant differences in serotonin uptake and release were observed between Wistar and FHR rat platelets.
- No differences were found in the predicted amino acid sequence of the serotonin transporter gene between the two rat strains.
- The coding sequence of the serotonin transporter in FHR has not been previously reported.
Conclusions:
- Differences in the primary structure of the serotonin transporter gene do not explain the altered serotonin storage observed in the FHR strain.
- The genetic basis for impaired serotonin storage in FHR likely lies in regulatory elements or other genes.
- Further research is needed to elucidate the genetic mechanisms underlying FHR's phenotype.