Synj1-flox Mouse

Synj1, short for Synaptojanin1, is a phosphoinositide phosphatase with dual SAC1 and 5'-phosphatase enzymatic activities. It is crucial for regulating phospholipid signaling and participates in synaptic vesicle (SV) recycling in neurons [2].

In mouse models, Synj1 heterozygous deletion (Synj1+/-) leads to PD-like pathologies. Male Synj1+/- mice show age-dependent motor function abnormalities, alpha-synuclein accumulation, impaired autophagy and dopaminergic terminal degeneration. Elevated 5'-phosphatase substrate, PI(4,5)P2, is found in midbrain neurons of Synj1+/- mice, and pharmacological elevation of membrane PI(4,5)P2 impairs SV endocytosis, especially in midbrain neurons, exacerbating SV trafficking defects [2]. Overexpression of SYNJ1 in hSNCA*A53T-Tg and MPTP-induced mice can rescue motor functions by upregulating TSP-1 expression, which is involved in the extracellular matrix pathways [1].

In conclusion, Synj1 is essential for synaptic vesicle recycling and phospholipid signaling in neurons. Studies on Synj1 KO/CKO mouse models have revealed its significant role in Parkinson's disease, showing that its deficiency can cause PD-like pathologies, while its overexpression may have a protective effect, providing potential therapeutic targets for PD [1,2].