Tmod2-flox Mouse

Tmod2, short for Tropomodulin 2, is an actin-regulating gene. It plays a crucial role in synapse maturation, dendritic arborization, and actin filament regulation by capping the slow-growing (pointed) end of actin filaments in a tropomyosin-dependent manner. These functions are essential for the development and function of neurons, and it is associated with pathways related to neural development and plasticity [2,3].

In Tmod2 knockout mouse models, the animals show emotionality phenotypes predictive of addiction vulnerability. Tmod2 deletion does not impact the acute locomotor response to cocaine but highly attenuates the sensitized locomotor responses, indicating perturbed drug-induced plasticity. Also, Tmod2 mutant animals do not self-administer cocaine, lacking hedonic responses. Electrophysiological characterization shows increased spontaneous firing rate of early postnatal and adult cortical and striatal neurons, and cocaine-induced synaptic plasticity is either missing or reciprocal in Tmod2 KO nucleus accumbens shell medium spiny neurons. This reveals Tmod2 as a major regulator of plasticity in the mesolimbic system, regulating the reinforcing and addictive properties of cocaine [1].

In conclusion, Tmod2 is essential for neural development and synaptic plasticity, playing a key role in regulating the actin cytoskeleton in neurons. The Tmod2 KO mouse models have provided valuable insights into its role in cocaine-related addiction, highlighting its potential as a therapeutic target for addiction-related disorders.