Abstract
A mouse model for the fragile X syndrome, the most common form of inherited mental retardation, was generated a number of years ago. It shows characteristics compatible with the clinical symptoms of human patients. These include pathological changes such as macroorchidism, behavioral problems, and diminished visuo-spatial abilities. To investigate whether the fragile X syndrome is a potentially correctable disorder, several groups attempted to rescue the knockout mutation by introduction of an intact copy of the FMR1 gene in the knockout mouse. Two different types of rescue mice have been created by injection of constructs based on FMR1 cDNA or on FMR1 genomic DNA. Several pathological, behavioral and cognitive function tests were performed on these two different rescue mouse lines to compare their characteristics with those of the knockout and control littermates. Each rescue line resembled the control in some aspects though neither of the 2 lines was a full rescue, e.g. resemble the control in all aspects investigated. Thus, rescue of some aspects of the phenotype has been achieved by introduction of FMR1 constructs in the fragile X knockout mice. The results implicate that, even if FMR1 production is cell type specific, the quantity of the FMRP expression is highly critical as overproduction may have a harmful effect.
Keywords: X Syndrome, FMR1 gene, FMR1 cDNA, reading frame (ORF), KNOCKOUT MUTATION, Transgenesis, YAC VECTOR
Current Molecular Medicine
Title: Restoring the Phenotype of Fragile X Syndrome: Insight from the Mouse Model
Volume: 1 Issue: 4
Author(s): I. Gantois, C. E. Bakker, E. Reyniers, R. Willemsen, R. DHooge, P. P. De Deyn, B. A. Oostra and R. F. Kooy
Affiliation:
Keywords: X Syndrome, FMR1 gene, FMR1 cDNA, reading frame (ORF), KNOCKOUT MUTATION, Transgenesis, YAC VECTOR
Abstract: A mouse model for the fragile X syndrome, the most common form of inherited mental retardation, was generated a number of years ago. It shows characteristics compatible with the clinical symptoms of human patients. These include pathological changes such as macroorchidism, behavioral problems, and diminished visuo-spatial abilities. To investigate whether the fragile X syndrome is a potentially correctable disorder, several groups attempted to rescue the knockout mutation by introduction of an intact copy of the FMR1 gene in the knockout mouse. Two different types of rescue mice have been created by injection of constructs based on FMR1 cDNA or on FMR1 genomic DNA. Several pathological, behavioral and cognitive function tests were performed on these two different rescue mouse lines to compare their characteristics with those of the knockout and control littermates. Each rescue line resembled the control in some aspects though neither of the 2 lines was a full rescue, e.g. resemble the control in all aspects investigated. Thus, rescue of some aspects of the phenotype has been achieved by introduction of FMR1 constructs in the fragile X knockout mice. The results implicate that, even if FMR1 production is cell type specific, the quantity of the FMRP expression is highly critical as overproduction may have a harmful effect.
Export Options
About this article
Cite this article as:
Gantois I., Bakker E. C., Reyniers E., Willemsen R., DHooge R., De Deyn P. P., Oostra A. B. and Kooy F. R., Restoring the Phenotype of Fragile X Syndrome: Insight from the Mouse Model, Current Molecular Medicine 2001; 1 (4) . https://dx.doi.org/10.2174/1566524013363492
DOI https://dx.doi.org/10.2174/1566524013363492 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
![](/images/wayfinder.jpg)
- 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
-
The Stress Rheostat: An Interplay Between the Unfolded Protein Response (UPR) and Autophagy in Neurodegeneration
Current Molecular Medicine Cardio-Hepatic Metabolic Derangements and Valproic Acid
Current Clinical Pharmacology Medical Complications in Anorexia and Bulimia Nervosa
Endocrine, Metabolic & Immune Disorders - Drug Targets The Multiple Facets of Hematopoietic Stem Cells
Current Neurovascular Research CD248: Reviewing its Role in Health and Disease
Current Drug Targets Multiple Hormonal Dysregulation as Determinant of Low Physical Performance and Mobility in Older Persons
Current Pharmaceutical Design Central Insulin and Insulin-Like Growth Factor-1 Signaling - Implications for Diabetes Associated Dementia
Current Diabetes Reviews Dynamic Factors Controlling Targeting Nanocarriers to Vascular Endothelium
Current Drug Metabolism Reversal of HIV Drug Resistance and Novel Strategies to Curb HIV Infection: The Viral Infectivity Factor Vif as a Target and Tool of Therapy
Current Drug Targets Hydroxychloroquine Sulfate (Plaquenil): A Possible Candidate for Pandemic SARS-CoV-2 or (COVID-19) ?
Coronaviruses The Role of Reactive Species in Epileptogenesis and Influence of Antiepileptic Drug Therapy on Oxidative Stress
Current Neuropharmacology Commentary: A Myriad Aberrations on Information of Ontogeny of Drug Metabolizing Enzymes in the Pediatric Population: An Obstacle for Personalizing Drug Therapy in the Pediatric Population
Drug Metabolism Letters Molecular and Biochemical Features of the Mitochondrial Enzyme Ornithine Transcarbamylase: A Possible New Role as a Signaling Factor
Current Medicinal Chemistry Micronutrients at the Interface Between Inflammation and Infection Ascorbic Acid and Calciferol. Part 2: Calciferol and the Significance of Nutrient Supplements
Inflammation & Allergy - Drug Targets (Discontinued) Use of Radiopharmaceuticals for Diagnosis, Treatment, and Follow-Up of Differentiated Thyroid Carcinoma
Anti-Cancer Agents in Medicinal Chemistry Lipids and Lysosomes
Current Drug Metabolism Targeting Protozoan Parasite Metabolism: Glycolytic Enzymes in the Therapeutic Crosshairs
Current Medicinal Chemistry Antiphospholipid Antibody-Mediated Thrombotic Mechanisms in Antiphospholipid Syndrome: Towards Pathophysiology-Based Treatment
Current Pharmaceutical Design Potential Drug Targets on the HIV-1 Envelope Glycoproteins, gp120 and gp41
Current Pharmaceutical Design Induced Pluripotent Stem Cells as a Model for Therapy Personalization of Pediatric Patients: Disease Modeling and Drug Adverse Effects Prevention
Current Medicinal Chemistry