Shank3-flox Mouse

Shank3, a member of the Shank family proteins, is a synaptic scaffolding protein enriched in the postsynaptic density of excitatory synapses. It plays crucial roles in synapse formation, maturation, and maintenance, and is involved in pathways related to neuronal connectivity [1,2].

Shank3 mutant mice, including knockout (KO) and conditional knockout (CKO) models, have been instrumental in understanding its functions. These mice exhibit autistic-like behaviors such as impaired social interaction, repetitive behaviors, and self-injurious repetitive grooming [1,2]. There are also deficits in striatal synapses and cortico-striatal circuits [2]. In the anterior cingulate cortex, conditional knockout of Shank3 causes excitatory synaptic dysfunction and social interaction deficits [5]. Additionally, in the context of cerebral ischemia/reperfusion, conditional knockout of Shank3 in neurons aggravates neuronal injuries [3]. In aging mice, cardiac-specific conditional knockout of Shank3 alleviates cardiac dysfunction by promoting Parkin-mediated mitophagy [4]. Shank3 deficiency in vagal sensory neurons affects body temperature regulation, systemic inflammation, and sepsis [6].

In conclusion, Shank3 is essential for normal neuronal connectivity and synaptic function. The use of Shank3 KO and CKO mouse models has significantly contributed to understanding its role in autism-spectrum disorders, as well as in other conditions like cerebral ischemia/reperfusion, cardiac aging, and inflammation regulation.