神經退化
Neurodegenerative Disease:
因老化造成神經細胞的死亡，導致神經功能的喪失或混亂。在模式動物上，經由行為學的測試可以檢驗其神經功能方面的缺失，而由組織解剖學的分析可得知神經退化的程度。另外，由於血腦屏障的作用，藥物的施用可分為腹腔、靜脈、皮下注射和立體定位手術。 我們熟知特性並能提供服務的模式動物有：
| Disease | Model | Phenotype |
| Alzheimer Disease | 3xTg-AD (homozygous for the Psen1 mutation and homozygous for the co-injected APPSwe and tauP301L transgenes) | 3xTg-AD (homozygous for the Psen1 mutation and homozygous for the co-injected APPSwe and tauP301L transgenes) The initial characterization of this mouse line indicated a progressive increase in amyloid beta peptide deposition, with intracellular immunoreactivity being detected in some brain regions as early as 3-4 months. Synaptic transmission and long-term potentiation are demonstrably impaired in mice 6 months of age. Between 12-15 months aggregates of conformationally altered and hyperphosphorylated tau are detected in the hippocampus. This mutant mouse exhibits plaque and tangle pathology associated with synaptic dysfunction, traits similar to those observed in Alzheimer's disease patients (from JAX). |
| Alzheimer Diseas | 5XFAD (human APP(695) with the Swedish (K670N, M671L), Florida (I716V), and London (V717I) Familial Alzheimer's Disease (FAD) mutations and human PS1 harboring two FAD mutations, M146L and L286V) | 5XFAD mice generate Abeta-42 almost exclusively, rapidly accumulating massive cerebral levels. On the mixed C57BL/6 and SJL background (see MMRRC stock 34840, intraneuronal Abeta-42 accumulation is observed starting at 1.5 months of age, just prior to amyloid deposition and gliosis, which begins at two months of age. On a congenic C57BL/6J genetic background (see MMRRC stock 34848) it has been the observation of the MMRRC that this phenotype is not as robust as that demonstrated in the mixed C57BL/6 and SJL background (view data). In addition, these mice have reduced synaptic marker protein levels, increased p25 levels, neuron loss, and memory impairment in the Y-maze test. 5XFAD transgenic mice recapitulate major features of Alzheimer's Disease amyloid pathology and may be useful models of intraneuronal Abeta-42 induced neurodegeneration and amyloid plaque formation (from JAX). |
| Huntington Disease | R6/2 (Mutant human huntingtin fragment containing ~1 kb of 5' UTR region and a polyglutamate-repeat (CAG) expansion of 160 +/- 5, and 262 bp of intron 1)) | Neuronal intranuclear inclusions, choreiform-like and involuntary stereotypic movements, tremors, and epileptic seizures by 9-11 weeks (from JAX). |
| ALS | SOD1 (Human SOD1 with glycine to alanine transition at position 93) | Decreased grip strength, impaired coordination, motor neuron degeneration, severe muscle weakness beyond 3 months old, hind limb tremors at 14 weeks old, become paralyzed in one or more limbs (from JAX). |
