IP3R2 null mice display a normal acquisition of somatic and neurological development milestones. (6th April 2020)

• Record Type: Journal Article
• Authors: Guerra‐Gomes, Sónia; Cunha‐Garcia, Daniela; Marques Nascimento, Diana Sofia; Duarte‐Silva, Sara; Loureiro‐Campos, Eduardo; Morais Sardinha, Vanessa; Viana, João Filipe; Sousa, Nuno; Maciel, Patrícia; Pinto, Luísa; Oliveira, João Filipe
• Other Names: Majewska Ania guestEditor.; Verkhratsky Alexej guestEditor.; Hughes Ethan guestEditor.
• Is Part Of: European journal of neuroscience. Volume 54:Number 5(2021)
• Page Start: 5673
• Page End: 5686
• Publication Date: 2020-04-06
• Subjects: astrocytes -- behaviour -- calcium signalling -- development -- IP3R2; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.14724
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: 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 (Ca 2+ ) levels. These astrocytic Ca 2+ elevations emerge from different sources and display complex spatio‐temporal properties. Ca 2+ 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 Ca 2+ 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 Ca 2+ elevations. Abstract : IP3 R2 KO mice lack global Ca 2+ elevations in astrocytes, but the constitutive receptor deletion during development may trigger compensating phenotypes, biasing experimental results. We show that male and female IP3 R2 KO mice display a normal acquisition of developmental milestones and present normal motor coordination, strength and neurological reflexes in adulthood. We also show that along with the complete deletion of Itpr2, there is no compensatory expression of Itpr1 or Itrp3 .