aip Mutant Zebrafish Display a Pseudo-Hypoxic Response Associated with Stress-Induced Hematopoiesis

The Ahr Interacting Protein (AIP), also known as XAP2 and ARA9, is a molecular chaperone essential for the cytosolic retention and stabilization of the AHR. Past studies, and AIP-linked human pathologies, suggest an alternative developmental role of the AIP apart from the AHR and canonical xenobiotic response.

A null mutation of the AIP in zebrafish larvae (designated as aipwh86) resulted in craniofacial malformations, failure to inflate the swim bladder, and an enlarged and darkened liver, emerging at 5–6-days post-fertilization (dpf). Histopathological analysis at 5 dpf suggested no histological differences in the homozygous (HMZ) mutant compared to wild type (WT). Whole-larvae RNA sequencing at 6 and 7 dpf showed significant dysregulation of key transcripts in the mutant larvae compared to WT, with pathway analysis revealing alterations in embryonic hematopoiesis and cardiac development.