Loss of TMEM106B and PGRN leads to severe lysosomal abnormalities and neurodegeneration in mice

ABSTRACT: Haploinsufficiency of progranulin (PGRN) is a leading cause of frontotemporal lobar degeneration (FTLD). Loss of PGRN leads to lysosome dysfunction during aging. TMEM106B, a gene encoding a lysosomal membrane protein, is the main risk factor for FTLD with PGRN haploinsufficiency. But how TMEM106B affects FTLD disease progression remains to be determined. Here we report that TMEM106B deficiency in mice leads to accumulation of lysosome vacuoles at the distal end of the axon initial segment in motor neurons and the development of FTLD related pathology during aging. Ablation of both PGRN and TMEM106B in mice results in severe neuronal loss and microglia and astrocyte activation in the spinal cord, retina and brain. Enlarged lysosomes are frequently found in both microglia and astrocytes. L

SUBMITTER: Dr. Tuancheng Feng 

PROVIDER: S-SCDT-EMBOR-2020-50219V1 | biostudies-other |

REPOSITORIES: biostudies-other