Related Experiment Video
Updated: Aug 10, 2026
Expression Analysis of Mammalian Linker-histone Subtypes
Published on: March 19, 2012
Cloning and expression of the mouse histamine H3 receptor: evidence for multiple isoforms
Agnès Rouleau1, Anne Héron, Véronique Cochois
1Unité de Neurobiologie et Pharmacologie Moléculaire (U573) de l'INSERM, Centre Paul Broca, Paris, France.
Abstract:
The existence of mouse H3-receptor isoforms was investigated by PCR analysis and cDNA cloning. Splicing mechanisms previously reported in various species are conserved in the mouse. The retention/deletion of a fragment in the third intracellular loop of the mouse receptor leads to the existence of three isoforms designated mH(3(445)), mH(3(413)) and mH(3(397)) according to the length of their deduced amino acid sequence. PCR analysis showed that mouse H3-receptor isoforms display different expression patterns in the brain. Following expression in Cos-1 cells, [125I]iodoproxyfan binding indicated similar pharmacological profiles of the mH(3(445)), mH(3(413)) and mH(3(397)) isoforms. The pharmacological profile of the mouse H3 receptor is more similar to the rat receptor than to the human receptor, although some differences were also observed between the mouse and rat receptors. For example, the potency of thioperamide and ciproxifan is slightly higher at the mouse receptor than at the rat receptor but 40-100-fold higher than at the human receptor. In situ hybridization histochemistry showed that the distribution of H3-receptor mRNAs in the mouse brain is rather similar to that previously reported in the rat brain. However, the autoradiographic and cellular expression patterns observed in several brain areas such as the thalamus or hippocampus reveal important differences between the two species.
Insights
Researchers identified three mouse H3 receptor isoforms (mH3(445), mH3(413), mH3(397)) due to conserved splicing. These isoforms show distinct brain expression patterns but similar pharmacology, closely resembling rat receptors.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Histamine H3 receptors are G protein-coupled receptors involved in neurotransmission.
- Receptor diversity arises from alternative splicing, impacting function and distribution.
- Understanding species-specific receptor characteristics is crucial for drug development.
Purpose of the Study:
- To investigate the existence and characteristics of mouse histamine H3 receptor (H3R) isoforms.
- To compare the pharmacological profiles and brain expression patterns of mouse H3R isoforms with those of rat and human receptors.
Main Methods:
- Polymerase Chain Reaction (PCR) and cDNA cloning to identify H3R isoforms.
- Expression in Cos-1 cells followed by radioligand binding assays ([125I]iodoproxyfan) for pharmacological profiling.
- In situ hybridization histochemistry and autoradiography to determine mRNA distribution and receptor expression patterns in the mouse brain.
Main Results:
- Three mouse H3R isoforms (mH3(445), mH3(413), mH3(397)) were identified, resulting from alternative splicing in the third intracellular loop.
- All three mouse H3R isoforms exhibited similar pharmacological profiles.
- Mouse H3R displayed a pharmacological profile more similar to rat H3R than human H3R, with notable differences in potency for certain ligands (thioperamide, ciproxifan).
- While H3R mRNA distribution was similar to rats, specific brain regions showed distinct autoradiographic and cellular expression patterns between mouse and rat.
Conclusions:
- Conserved splicing mechanisms generate multiple mouse H3R isoforms with distinct expression patterns but conserved pharmacology.
- Mouse H3R characteristics are more akin to rat H3R, suggesting species-specific variations in histamineergic neurotransmission.
- These findings provide valuable insights into the molecular diversity and species-specific regulation of H3 receptors.
More Related Videos
07:30HSV-Mediated Transgene Expression of Chimeric Constructs to Study Behavioral Function of GPCR Heteromers in Mice
Published on: July 9, 2016
08:16Detection of G Protein-coupled Receptor Expression in Mouse Vagal Afferent Neurons using Multiplex In Situ Hybridization
Published on: September 20, 2021
