Publicação
IP3R2 null mice display a normal acquisition of somatic and neurological development milestones
| Resumo: | 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<sup>2+</sup>) levels. These astrocytic Ca<sup>2+</sup> elevations emerge from different sources and display complex spatio-temporal properties. Ca<sup>2+</sup> 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 (IP<inf>3</inf>R2 KO) mouse model lacks global Ca<sup>2+</sup> elevations in astrocytes, and it has been used by different laboratories. However, the constitutive deletion of IP<inf>3</inf>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 IP<inf>3</inf>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 IP<inf>3</inf>R2 KO mice display a normal acquisition of developmental milestones, as compared with wild-type (WT) mice. We also show that IP<inf>3</inf>R2 KO mice display normal motor coordination, strength and neurological reflexes in adulthood. To exclude a potential compensatory overexpression of other IP<inf>3</inf>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 IP<inf>3</inf>R2 KO mouse is a reliable model to study the functional impact of global IP<inf>3</inf>R2-dependent astrocytic Ca<sup>2+</sup> elevations. |
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| Autores principais: | Gomes, Sónia Isabel Nunes Guerra |
| Outros Autores: | Garcia, Daniela Raquel Cunha; Nascimento, Diana Sofia Marques; Silva, Sara Carina Duarte; Loureiro-Campos, Eduardo; Sardinha, Vanessa Alexandra Morais; Viana, João Filipe Oliveira; Sousa, Nuno; Maciel, P.; Pinto, Luísa; Oliveira, João F. |
| Assunto: | astrocytes behaviour calcium signalling development IP3R2 |
| Ano: | 2021 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | 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<sup>2+</sup>) levels. These astrocytic Ca<sup>2+</sup> elevations emerge from different sources and display complex spatio-temporal properties. Ca<sup>2+</sup> 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 (IP<inf>3</inf>R2 KO) mouse model lacks global Ca<sup>2+</sup> elevations in astrocytes, and it has been used by different laboratories. However, the constitutive deletion of IP<inf>3</inf>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 IP<inf>3</inf>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 IP<inf>3</inf>R2 KO mice display a normal acquisition of developmental milestones, as compared with wild-type (WT) mice. We also show that IP<inf>3</inf>R2 KO mice display normal motor coordination, strength and neurological reflexes in adulthood. To exclude a potential compensatory overexpression of other IP<inf>3</inf>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 IP<inf>3</inf>R2 KO mouse is a reliable model to study the functional impact of global IP<inf>3</inf>R2-dependent astrocytic Ca<sup>2+</sup> elevations. |
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