Panx1 forms plasma membrane channels in brain and several other organs, including the inner ear. Biophysical properties, activation mechanisms and modulators of Panx1 channels have been characterized in detail, however the impact of Panx1 on auditory function is unclear due to conflicts in published results. To address this issue, hearing performance and cochlear function of the Panx1−/− mouse strain, the first with a reported global ablation of Panx1, were scrutinized. Male and female homozygous (Panx1−/−), hemizygous (Panx1+/−) and their wild type (WT) siblings (Panx1+/+) were used for this study. Successful ablation of Panx1 was confirmed by RT-PCR and Western immunoblotting in the cochlea and brain of Panx1−/− mice. Furthermore, a previously validated Panx1-selective antibody revealed strong immunoreactivity in WT but not in Panx1−/− cochleae. Hearing sensitivity, outer hair cell-based “cochlear amplifier” and cochlear nerve function, analyzed by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) recordings, were normal in Panx1+/− and Panx1−/− mice. In addition, we determined that global deletion of Panx1 impacts neither on connexin expression, nor on gap-junction coupling in the developing organ of Corti. Finally, spontaneous intercellular Ca²⁺ signal (ICS) activity in organotypic cochlear cultures, which is key to postnatal development of the organ of Corti and essential for hearing acquisition, was not affected by Panx1 ablation. Therefore, our results provide strong evidence that, in mice, Panx1 is dispensable for hearing acquisition and auditory function.

Odad3 gene loss-of-function mutation leads to Primary Ciliary Dyskinesia (PCD), a disease caused by motile cilia dysfunction. Previously, we demonstrated that knockout of the Odad3 gene in mice replicates several features of PCD, such as hydrocephalus, defects in left–right body symmetry, and male infertility, with a complete absence of sperm in the reproductive tract. The majority of Odad3 knockout animals die before sexual maturation due to severe hydrocephalus and failure to thrive, which precludes fertility studies. Here, we performed the expression analysis of the Odad3 gene during gonad development and in adult testes. We showed that Odad3 starts its expression during the first wave of spermatogenesis, specifically at the meiotic stage, and that its expression is restricted to the germ cells in the adult testes, suggesting that Odad3 plays a role in spermatozoa formation. Subsequently, we conditionally deleted the Odad3 gene in adult males and demonstrated that even partial ablation of the Odad3 gene leads to asthenoteratozoospermia with multiple morphological abnormalities of sperm flagella (MMAF) in mice. The analysis of the seminiferous tubules in Odad3-deficient mice revealed defects in spermatogenesis with accumulation of seminiferous tubules at the spermiogenesis and spermiation phases. Furthermore, analysis of fertility in heterozygous Odad3^+/− knockout mice revealed a reduction in sperm count and motility as well as abnormal sperm morphology. Additionally, Odad3^+/− males exhibited a shorter fertile lifespan. Overall, these results suggest the important role of Odad3 and Odad3 gene dosage in male fertility. These findings may have an impact on the genetic and fertility counseling practice of PCD patients carrying Odad3 loss-of-function mutations.

Background/Objectives: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired ciliary function, leading to chronic airway disease. Loss-of-function mutations in ODAD3 (CCDC151) represent an established cause in patients, and Odad3-deficient mice recapitulate key disease traits. However, the impact of Odad3 ablation on upper airway development and function remains unexplored. This study investigated the consequences of Odad3 disruption on upper airway structures during development and in adult animals. Methods: Constitutive (Odad3^−/−) and inducible conditional (Odad3^icKO) mouse models were analyzed alongside heterozygous and wild-type littermates during embryonic, postnatal, and adult stages. Optimized high-resolution 3D micro-computed tomography (micro-CT or µCT) combined with histology was utilized to conduct systematic genotype-phenotype evaluations, map upper airway anatomical architecture, and assess PCD disease onset. Results: Genetic dissection revealed a marked dependence of the phenotype on whether Odad3 loss occurred during development or in adulthood. Constitutive Odad3 deletion resulted in pervasive craniofacial remodeling and turbinate hypoplasia during embryonic stages and early postnatal development. Conversely, adult-induced conditional ablation produced localized caudal atrophy of the nasal turbinates accompanied by massive mucus accumulation, consistent with impaired mucociliary clearance and providing a 3D structural and morphological characterization of chronic rhinosinusitis-like pathology in PCD mouse models. Heterozygous Odad3^icKO/+ and Odad3^+/− mice were phenotypically indistinguishable from wild-type controls, indicating that single-allele loss does not disrupt upper airway morphology. Conclusions: This study characterizes the structural timeline of upper airway pathology in PCD and validates the Odad3^icKO model as a robust 3D structural phenotyping platform for investigating airway disease in ciliopathies. Combining targeted genetic disruption with 3D µCT virtual histology offers a powerful framework for comprehensive studies of human genetic variants and gene knockouts in mouse models of PCD.