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IP 3 R2 null mice display a normal acquisition of somatic and neurological development milestones
Author(s) -
GuerraGomes Sónia,
CunhaGarcia Daniela,
Marques Nascimento Diana Sofia,
DuarteSilva Sara,
LoureiroCampos Eduardo,
Morais Sardinha Vanessa,
Viana João Filipe,
Sousa Nuno,
Maciel Patrícia,
Pinto Luísa,
Oliveira João Filipe
Publication year - 2021
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.14724
Subject(s) - knockout mouse , neuroscience , biology , phenotype , somatic cell , receptor , reflex , medicine , endocrinology , gene , genetics
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 (IP 3 R2 KO) mouse model lacks global Ca 2+ elevations in astrocytes, and it has been used by different laboratories. However, the constitutive deletion of IP 3 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 3 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 3 R2 KO mice display a normal acquisition of developmental milestones, as compared with wild‐type (WT) mice. We also show that IP 3 R2 KO mice display normal motor coordination, strength and neurological reflexes in adulthood. To exclude a potential compensatory overexpression of other IP 3 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 3 R2 KO mouse is a reliable model to study the functional impact of global IP 3 R2‐dependent astrocytic Ca 2+ elevations.