Large Animal Models For Neururodegenerative Diseases Case...

Large animal models for neurodegenerative diseases Numerous human genetic disorders, such as neurodegenerative diseases, occur because of genetic mutations in human cells. New genome editing tools – as of 2014 - such as transcription activator-like endonucleases (TALENs) or CRISPR/Cas9 further ease the precise generation of non-human primates (NHP) models for human diseases. Several of these NHP models displayed clinical manifestations like those of human disorders, in comparison with rodent models. These new techniques are efficient, as well as easy to conduct. They also exhibit a low rate of off-targeting, allow the knockout of multiple genes, and can create bi-allelic mutants. Several species of large animals were utilized to generate†¦show more content†¦Nuclear transfer was used to generate transgenic pigs that expressed the N-terminal region of mutant HTT (including 1–208 amino acids) composed of 105 repeats of glutamine residue. Among the five piglets, three of them died after 3 days of birth and the fourth died after 25 days. Only one offspring remained alive that did not show any pathological signs at four months of age. The mHTT expression levels was markedly different between piglets [41]. Generation of HD animal models using random intra genomic insertion of the mutant HTT may lead to function disrupting of the other neighbor genes. The destruction of these genes may influence the phenotypes caused by mHTT or may result in a lethal mutation before the manifestation of desired phenotype [43]. Amyotrophic lateral sclerosis (ALS) ALS disease often manifests in early adulthood and is associated with loss of motor neurons in the cortex , spinal cord, and brainstem [44, 45]. ALS leads to progressive weakness of autonomic muscles. Death typically results due diaphragmatic failure within 2–5 years. Sporadic type of this disorder is prevalent and the incidence rate of hereditary forms of ALS is accounted for 5 to 10 percent of patients. Hereditary ALS could result by infusions in sarcoma (FUS), superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP-43), and C9ORF72 mutations. SOD1 mutation solely account for ~2% of ALS patients. Pig models have been created which