Double deletion of Panx1 and Panx3 affects skin and bone but not hearing
Pannexins (Panxs), large-pore channel forming glycoproteins, are expressed in a wide variety of tissues including the skin, bone, and cochlea. To date, the use of single knock-out mouse models of both Panx1 and Panx3 have demonstrated their roles in skin development, bone formation, and auditory phenotypes. Due to sequence homology between Panx1 and Panx3, when one Panx is ablated from germline, the other may be upregulated in a compensatory mechanism to maintain tissue homeostasis and function. To evaluate the roles of Panx1 and Panx3 in the skin, bone, and cochlea, we created the first Panx1/Panx3 double knock-out mouse model (dKO). These mice had smaller litters and reduced body weight compared to wildtype controls. The dKO dorsal skin had decreased epidermal and dermal area as well as decreased hypodermal area in neonatal but not in older mice. In addition, mouse skull shape and size were altered, and long bone length was decreased in neonatal dKO mice. Finally, auditory tests revealed that dKO mice did not exhibit hearing loss and were even slightly protected against noise-induced hearing damage at mid-frequency regions. Taken together, our findings suggest that Panx1 and Panx3 are important at early stages of development in the skin and bone but may be redundant in the auditory system.
Panx double KO mice had smaller litters and reduced body weight.
dKO skin had decreased epidermal and dermal area in neonatal mice.
Skull shape and size changed plus long bone length decreased in neonatal dKO mice.
dKO had no hearing loss and were slightly protected against noise-induced damage.
KeywordsPannexin Hearing Skin Bone Panx1 Panx3
We thank Genentech Inc. (San Francisco, CA) for the gift of the Panx1 knockout mouse, Rafael Sanchez Pupo for technical assistance, and Quintyn Farrar for his help collecting long bone data. JMA was funded by a Natural Sciences and Engineering Research Council (NSERC) Scholarship. BO and CBW were funded by an Ontario Graduate Scholarship (OGS). EJ and CBW received the Collaborative Specialization in Musculoskeletal Health Research (CMHR) award. NSERC Discovery Grant to KW. CIHR Project grant to BLA. NSERC Discovery Grant to SP.
JMA: Mouse genotyping, conducted all hearing experiments, data collection, and analysis, compilation of all experimental data, and wrote the manuscript draft.
BO’D: Mouse genotyping, expression analyses of skin and hindlimb, histological analyses of skin and paw.
CBW: Mouse genotyping, qPCR and protein experiments, data collection, and analysis.
EJ: Skull data collection and analysis, histological analysis of tibial growth plate and long bone cross-sectional analyses.
JJK: Conceptualization of the dKO hearing study, student training, data analysis.
KB: Generated the dKO mice, performed initial characterization and limb bone length comparisons, and contributed to skull landmarking.
KW: Skull and limb phenotypic analyses, provided funding.
BLA: Analyses and interpretation of hearing testing, provided funding.
SP: Generation of the dKO mice, initial characterization experiments, study design, provided funding, supervised and coordinated all participants, data analysis, manuscript editing.
All authors participated in manuscript editing.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
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