Cell and sub-compartment specific proteomics reveals astrocyte contributions in a mouse model of OCD

We investigated the sub-proteomes of different functional compartments in astrocyte and neurons in the striatum. We compared the proteomes to the cell-specific RNA profiles of neurons and astrocytes from these analyses. We found one gene and protein that was highly expressed in neurons and astrocytes called SAPAP3. Knockout of this gene product results in an OCD-like phenotype in mouse. RNA-seq of astrocytes and bulk RNA-seq analyses of this mouse model revealed very low DEGs. 40 samples from 24 adult mice. Astrocyte RiboTag AAV and Neuron RiboTag AAV was injected into the striatum to extract RNA specifically from astrocytes or neurons. We used wildtype mice and used an OCD mouse model (SAPAP3 KO). After tissue homogenization, RNA was purified from the cleared lysate as the input sample and astrocyte or neuron specific ribosome-associated RNA was immunoprecipitated with a hemagglutinin (HA) tag as the IP sample.