Lack of Stim2 Affects Vision-Dependent Behavior and Sensitivity to Hypoxia.

Stromal interaction molecules (STIMs) are endoplasmic reticulum-resident proteins that regulate Ca 2+ homeostasis and signaling by store-operated calcium entry (SOCE). The different properties and functions of STIM1 and STIM2 have been described mostly based on work in vitro . STIM2 knockout mice do not survive until adulthood. Therefore, we generated and characterized stim2a and stim2b double-knockout zebrafish. The ( stim2a;stim2b ) -/- zebrafish did not have any apparent morphological phenotype. However, RNA sequencing revealed 1424 differentially expressed genes. One of the most upregulated genes was annexin A3a , which is a marker of activated microglia. This corresponded well to an increase in Neutral Red staining in the in vivo imaging of the ( stim2a;stim2b ) -/- zebrafish brain. The lack of Stim2 decreased zebrafish survival under low oxygen conditions. Behavioral tests, such as the visual-motor response test and dark-light preference test, indicated that ( stim2a;stim2b ) -/- larvae might have problems with vision. This was consistent with the downregulation of many genes that are related to light perception. The periodic acid-Schiff staining of retina sections from adult zebrafish revealed alterations of the stratum pigmentosum, suggesting the involvement of a Stim2-dependent process in visual perception. Altogether, these data reveal new functions for Stim2 in the nervous system.