Generation and analysis of FUS and TMEM106B mouse models.

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD) are two devastating adult onset neurodegenerative disorders. In ALS patients FUS mutations were found as a primary cause. For FTLD-TDP, TMEM106B was identified to be a risk factor. To gain more insight into the pathomechanisms, mouse models for FUS and TMEM106B should be generated and analyzed. Regarding FUS, mice should express different ALS associated mutations and be compared with Fus deficient mice, as it is unclear if FUS causes ALS via a loss or a gain of function model. Since TMEM106B was reported to be elevated in patients, a mouse model should be generated, overexpressing Tmem106b. Summarizing the results, FUS mouse lines were partly inhomogenous and there is no clear evidence for a loss of function model. Taken together, FUS and TMEM106B mouse models could not mimic ALS or FTLD. However, results provided evidence, that mitochondria and mitophagy play an important role in both diseases