SPLA2-IIA modifies progranulin deficiency phenotypes in mouse models.

ABSTRACT:

Background

Haploinsufficiency of the progranulin (PGRN) protein is a leading cause of frontotemporal lobar degeneration (FTLD). Mouse models have been developed to study PGRN functions. However, PGRN deficiency in the commonly used C57BL/6 mouse strain background leads to very mild phenotypes, and pathways regulating PGRN deficiency phenotypes remain to be elucidated.

Methods

We generated PGRN-deficient mice in the FVB/N background and compared PGRN deficiency phenotypes between C57BL/6 and FVB/N backgrounds via immunostaining, western blot, RNA-seq, and proteomics approaches. We demonstrated a novel pathway in modifying PGRN deficiency phenotypes using inhibitor treatment and AAV-mediated overexpression in mouse models.

Results

We report that PGRN loss in the FVB/N m

SUBMITTER: Yang C 

PROVIDER: S-EPMC12175356 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature