Abstract
Using gene knockout mice of particular genes is one of the most effective methods in conducting successful study on the mode of action of target gene products in targeted organs. So called the knockout technology is now a powerful tool that can lead us to find clear understanding on difficult questions such as the effects of full antagonist against target molecules. Cacna1b ( 1B) gene knockout mouse was generated to study mechanisms of N-type calcium (Ca2+) channel. The model was able to overcome physiological obstacles in studies of N-type Ca2+ channel selective blockers, such as unspecific binding to structurally similar molecules, and failed distribution to targeted organs. In the case of N-type Ca2+ channel studies, knockout technology was successfully applied to various cardiovascular, sympathetic, nociceptive, sleepawake cycles, metabolic and neurodegenerative experiments using homozygous mutants of the 1B gene that turned out to be viable. These studies were able to confirm not only the predicted phenotypes, but were able to present completely unexpected phenotypes that are great interest for future study. Thus the outputs from the knockout mouse studies lead to gain the proof of concept as a drug for specific inhibitors of the gene products and enabled us to make further prediction of side-effects of these inhibitors in the drug discovery and development process.
Keywords: Drug Discovery Process, gene knockout mice, calcium (Ca2+) channel, phenotypes, inhibitors
Current Pharmaceutical Biotechnology
Title: The Utilization of Gene Targeting Models During in Preclinical Study of Drug Discovery Process - Example of Phenotypic and Functional Analysis of Cacna1 βGene Product
Volume: 10 Issue: 2
Author(s): Norimasa Miyamoto, Kana Namiki, Naoki Tokuhara, Mai Uesugi, Eiki Takahashi, Junro Kuromitsu and Yoshitoshi Kasuya
Affiliation:
Keywords: Drug Discovery Process, gene knockout mice, calcium (Ca2+) channel, phenotypes, inhibitors
Abstract: Using gene knockout mice of particular genes is one of the most effective methods in conducting successful study on the mode of action of target gene products in targeted organs. So called the knockout technology is now a powerful tool that can lead us to find clear understanding on difficult questions such as the effects of full antagonist against target molecules. Cacna1b ( 1B) gene knockout mouse was generated to study mechanisms of N-type calcium (Ca2+) channel. The model was able to overcome physiological obstacles in studies of N-type Ca2+ channel selective blockers, such as unspecific binding to structurally similar molecules, and failed distribution to targeted organs. In the case of N-type Ca2+ channel studies, knockout technology was successfully applied to various cardiovascular, sympathetic, nociceptive, sleepawake cycles, metabolic and neurodegenerative experiments using homozygous mutants of the 1B gene that turned out to be viable. These studies were able to confirm not only the predicted phenotypes, but were able to present completely unexpected phenotypes that are great interest for future study. Thus the outputs from the knockout mouse studies lead to gain the proof of concept as a drug for specific inhibitors of the gene products and enabled us to make further prediction of side-effects of these inhibitors in the drug discovery and development process.
Export Options
About this article
Cite this article as:
Miyamoto Norimasa, Namiki Kana, Tokuhara Naoki, Uesugi Mai, Takahashi Eiki, Kuromitsu Junro and Kasuya Yoshitoshi, The Utilization of Gene Targeting Models During in Preclinical Study of Drug Discovery Process - Example of Phenotypic and Functional Analysis of Cacna1 βGene Product, Current Pharmaceutical Biotechnology 2009; 10 (2) . https://dx.doi.org/10.2174/138920109787314999
DOI https://dx.doi.org/10.2174/138920109787314999 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
Call for Papers in Thematic Issues
Artificial Intelligence in Bioinformatics
Bioinformatics is an interdisciplinary field that analyzes and explores biological data. This field combines biology and information system. Artificial Intelligence (AI) has attracted great attention as it tries to replicate human intelligence. It has become common technology for analyzing and solving complex data and problems and encompasses sub-fields of machine ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Uracils as a Cellular Weapon Against Viruses and Mechanisms of Viral Escape
Current HIV Research Ideational Fluency in Patients with Rheumatoid Arthritis
Current Rheumatology Reviews The Pathology Induced by Highly Active Antiretroviral Therapy Against Human Immunodeficiency Virus: an Update
Current Medicinal Chemistry Listeria-Based Anti-Infective Vaccine Strategies
Recent Patents on Anti-Infective Drug Discovery Trends and Applications of Brain Computer Interfaces
Current Signal Transduction Therapy Biomedical Perspectives of Acute and Chronic Neurological and Neuropsychiatric Sequelae of COVID-19
Current Neuropharmacology Cerebral Amyloidoses: Molecular Pathways and Therapeutic Challenges
Current Medicinal Chemistry p38 MAP Kinase Inhibitors as Potential Therapeutic Drugs for Neural Diseases
Central Nervous System Agents in Medicinal Chemistry Editorial (Thematic Issue: Neuroglia as a Central Element of Neurological Diseases: An Underappreciated Target for Therapeutic Intervention)
Current Neuropharmacology Virus-Host Interactions: New Insights and Advances in Drug Development Against Viral Pathogens
Current Drug Metabolism A Coadunation of Biological and Mathematical Perspectives on the Pandemic COVID-19: A Review
Coronaviruses Neuroinflammation and Neuroprotection: An Update on (Future) Neurotrophin-Related Strategies in Multiple Sclerosis Treatment
Current Medicinal Chemistry Filariasis: Current Status, Treatment and Recent Advances in Drug Development
Current Medicinal Chemistry Small-Cell Lung Cancer: Clinical Management and Unmet Needs New Perspectives for an Old Problem
Current Drug Targets Functional Selectivity in Cannabinoid Signaling
Current Molecular Pharmacology Inactivation of Pathogenic Microorganisms by Photodynamic Techniques:Mechanistic Aspects and Perspective Applications.
Anti-Infective Agents in Medicinal Chemistry Demographic, Clinical and Laboratory Profiles of HIV Infected Patients Admitted into Imam Khomeini Hospital of Tehran, Iran
Infectious Disorders - Drug Targets What Animal Models are Best to Test Novel Rheumatoid Arthritis Therapies?
Current Rheumatology Reviews Safe and Effective Delivery of Amphotericin B: A Survey of Patents
Recent Patents on Nanotechnology Delineating Somatostatins Neuronal Actions
Current Drug Targets - CNS & Neurological Disorders