A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
| Autor: | Shao-Bin Wang, Brian Thompson, Victoria L. Patterson, Bo Chen, Josephine Hoh, Catherine Cherry |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Aging Genotype General Chemical Engineering Transgene Population Genome-wide association study Mice Transgenic Disease 01 natural sciences Polymorphism Single Nucleotide General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Mice Medicine Animals Humans Gene Knock-In Techniques education Mice Knockout education.field_of_study General Immunology and Microbiology business.industry General Neuroscience 010401 analytical chemistry Serine Endopeptidases Proteins High-Temperature Requirement A Serine Peptidase 1 Phenotype eye diseases 0104 chemical sciences Genetically modified organism Disease Models Animal 030104 developmental biology Factor H Complement Factor H HTRA1 Immunology business |
| Zdroj: | Journal of visualized experiments : JoVE. (113) |
| ISSN: | 1940-087X |
| Popis: | Age-related diseases are becoming increasingly prevalent and the burden continues to grow as our population ages. Effective treatments are necessary to lessen the impact of debilitating conditions but remain elusive in many cases. Only by understanding the causes and pathology of diseases associated with aging, can scientists begin to identify potential therapeutic targets and develop strategies for intervention. The most common age-related conditions are neurodegenerative disorders such as Parkinson's disease and blindness. Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Genome wide association studies have previously identified loci that are associated with increased susceptibility to this disease and identified two regions of interest: complement factor H (CFH) and the 10q26 locus, where the age-related maculopathy susceptibility 2 (ARMS2) and high-temperature requirement factor A1 (HtrA1) genes are located. CFH acts as a negative regulator of the alternative pathway (AP) of the complement system while HtrA1 is an extracellular serine protease. ARMS2 is located upstream of HtrA1 in the primate genome, although the gene is absent in mice. To study the effects of these genes, humanized knock-in mouse lines of Cfh and ARMS2, knockouts of Cfh, HtrA1, HtrA2, HtrA3 and HtrA4 as well as a conditional neural deletion of HtrA2 were generated. Of all the genetically engineered mice produced only mice lacking HtrA2, either systemically or in neural tissues, displayed clear phenotypes. In order to examine these mice thoroughly and systematically, an initial phenotyping schedule was established, consisting of a series of tests related to two main diseases of interest: AMD and Parkinson's. Genetically modified mice can be subjected to appropriate experiments to identify phenotypes that may be related to the associated diseases in humans. A phenotyping regimen with a mitochondrial focus is presented here alongside representative results from the tests of interest. |
| Databáze: | OpenAIRE |
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