The CD33 short isoform is a gain-of-function variant that enhances Aβ_1-42 phagocytosis in microglia.

ABSTRACT:

Background

CD33 is genetically linked to Alzheimer's disease (AD) susceptibility through differential expression of isoforms in microglia. The role of the human CD33 short isoform (hCD33m), preferentially encoded by an AD-protective CD33 allele (rs12459419T), is unknown. Here, we test whether hCD33m represents a loss-of-function or gain-of-function variant.

Methods

We have developed two models to test the role of hCD33m. The first is a new strain of transgenic mice expressing hCD33m in the microglial cell lineage. The second is U937 cells where the CD33 gene was disrupted by CRISPR/Cas9 and complemented with different variants of hCD33. Primary microglia and U937 cells were tested in phagocytosis assays and single cell RNA sequencing (scRNAseq) was carried out on the primary

SUBMITTER: Bhattacherjee A 

PROVIDER: S-EPMC7992807 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature