Transgenic mice expressing mutant prion proteins spontaneously develop neurologic dysfunction and spongiform neuropathology.
"Knock-in" mice expressing mutant GABAA subunits engineered to be insensitive to benzodiazepines or general anaesthetics have proved invaluable in evaluating the role of GABAA receptor subtypes in complex behaviours such as sedation, cognition and anxiety [Rudolph, U., Mohler, H., 2006. GABA-based therapproachesproaches: GABAA receptor subtype functions. Curr. Opin. Pharmacol. 6, 18 23].
Aberrant axonal transport contributes toward pathogenesis in sporadic ALS and in mice expressing mutant SOD1 [26] [28].
Conversely, mice expressing mutant tau associated with familial fronto-temporal dementia (FTD) recapitulate robust tauopathy [14] [17].
Transgenic mice expressing mutant forms of SOD1 (mice1 mice) recapitulate the phenotype of ALS and provide the only currently available faithful model of ALS [1], [2].
To test this, we crossed αB-crystallin/HspB2 deficient (CRYAB-/-HSPB2-/) mice with AD model transgenic mice expressing mutant human amyloid precursor protein.
Fibrillar inclusions containing SOD1 and SOD1 inclusions that bind the amyloid-specific dye thioflavin S have been found in neurons of transgenic mice expressing mutant SOD1.
A third study also showed that mice expressing mutant human MYOC (including Q368X and Y437H) in their eyes developed elevated intraocular pressure [44].
Interestingly, complex I proteins have been found to be deregulated in triple transgenic AD mice (expressing mutant tau, APP and PS1) which exhibit both Aβ and tau pathologies [16].
Glial cells are activated early in transgenic mice expressing mutant SOD1, suggesting that neuroinflammation has a relevant role in the cascade of events that trigger the death of motor neurons.
Previous studies using the pmn mouse model [35] and the Bax-deficient mice crossed with mice expressing mutant SOD1G93A [36] have shown that GDNF can protect motor neurons which are no longer connected to the muscle.
