Astrocytes are key players in the regulation of brain development and function. They sense and respond to the surrounding activity by elevating their intracellular calcium (Ca²⁺ ) levels. These astrocytic Ca²⁺ elevations emerge from different sources and display complex spatio-temporal properties. Ca²⁺ elevations are spatially distributed in global (soma and main processes) and/or focal regions (microdomains). The inositol 1,4,5-trisphosphate receptor type 2 knockout (IP₃ R2 KO) mouse model lacks global Ca²⁺ elevations in astrocytes, and it has been used by different laboratories. However, the constitutive deletion of IP₃ R2 during development may trigger compensating phenotypes, which could bias the results of experiments using developing or adult mice. To address this issue, we performed a detailed neurodevelopmental evaluation of male and female IP₃ R2 KO mice, during the first 21 days of life, as well as an evaluation of motor function, strength and neurological reflexes in adult mice. Our results show that male and female IP₃ R2 KO mice display a normal acquisition of developmental milestones, as compared with wild-type (WT) mice. We also show that IP₃ R2 KO mice display normal motor coordination, strength and neurological reflexes in adulthood. To exclude a potential compensatory overexpression of other IP₃ Rs, we quantified the relative mRNA levels of all 3 subtypes, in brain tissue. We found that, along with the complete deletion of Itpr2, there is no compensatory expression of Itpr1 or Itrp3. Overall, our results show that the IP₃ R2 KO mouse is a reliable model to study the functional impact of global IP₃ R2-dependent astrocytic Ca²⁺ elevations.

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