Knockout of Pannexin-1 Induces Hearing Loss

Chen, Jin; Liang, Chun; Zong, Lei; Zhu, Yan; Zhao, Hong-Bo

doi:10.3390/ijms19051332

Cited by 11 publications

(7 citation statements)

References 46 publications

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“…In contrast, another Panx1 −/− mouse had normal hearing and did not exhibit any auditory brainstem morphology deformities [26]. Recently, that same Panx1 −/− model was found to have mild hearing loss at low frequencies which was more pronounced at higher frequencies (i.e., 32 and 40 kHz) [45]. Zorzi and colleagues re-examined Fig.…”

Section: Discussionmentioning

confidence: 99%

Double deletion of Panx1 and Panx3 affects skin and bone but not hearing

et al. 2019

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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 knockout 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 knockout 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. Key messages & 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.

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Section: Discussionmentioning

confidence: 99%

Double deletion of Panx1 and Panx3 affects skin and bone but not hearing

et al. 2019

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“…Alachua, FL). As described in our previous reports [18,20], CM was evoked by the tone bursts (8-40 kHz). The response signal was filtered with a band-pass filter from 3 kHz to 50 kHz to filter out ABR signals, and averaged by 250 times.…”

Section: Cochlear Microphonics Recordingmentioning

confidence: 97%

Hearing loss is an early biomarker in APP/PS1 Alzheimer’s disease mice

Liu

Fang

Liu

et al. 2020

Neuroscience Letters

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Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive loss of memory and cognitive decline. Over the last decade, it has been found that defects in sensory systems could be highly associated with AD. Hearing is an important neural sense. However, little is known about hearing functional changes in AD. In this study, APP/PS1 AD mice (Jackson Lab: Stack No. 004462) were used. Hearing function was assessed by auditory brainstem response (ABR), distortion product otoacoustic emission (DPOAE), and cochlear microphonics (CM) recordings. Wild-type (WT) littermates served as control. We found that APP/PS1 AD mice measured as ABR threshold had hearing loss. The hearing loss appeared at high frequency as early as 2 months old, prior to the reported occurrence of spatial learning deficit at 6-7 months of age in this AD mouse model. The hearing loss was progressive and extended from high frequency to low frequency. At 3-4 months old, the hearing loss appeared in the whole-frequency range. Moreover, the wave IV and V in the super-threshold ABR were eliminated, indicating substantial impairment in inferior colliculus, nuclei of lateral lemniscus, and medial geniculate body in the upper brainstem. DPOAE in APP/PS1 AD mice was also reduced. However, there was no reduction in CM in APP/PS1 mice. These data demonstrate that unlike age-related hearing loss APP/PS1 AD

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“…CM was evoked by 8-kHz tone bursts and recorded with the same electrode setting as ABR recording as previously reported ( 16 , 23 , 35 ). The signal was amplified by 50,000 with 3- to 50-kHz filter and averaged by 100 times.…”

Section: Methodsmentioning

confidence: 99%

Cx26 heterozygous mutations cause hyperacusis-like hearing oversensitivity and increase susceptibility to noise

et al. 2023

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Gap junction gene GJB2 (Cx26) mutations cause >50% of nonsyndromic hearing loss. Its recessive hetero-mutation carriers, who have no deafness, occupy ~10 to 20% of the general population. Here, we report an unexpected finding that these heterozygote carriers have hearing oversensitivity, and active cochlear amplification increased. Mouse models show that Cx26 hetero-deletion reduced endocochlear potential generation in the cochlear lateral wall and caused outer hair cell electromotor protein prestin compensatively up-regulated to increase active cochlear amplification and hearing sensitivity. The increase of active cochlear amplification also increased sensitivity to noise; exposure to daily-level noise could cause Cx26 +/− mice permanent hearing threshold shift, leading to hearing loss. This study demonstrates that Cx26 recessive heterozygous mutations are not “harmless” for hearing as previously considered and can cause hyperacusis-like hearing oversensitivity. The data also indicate that GJB2 hetero-mutation carriers are vulnerable to noise and should avoid noise exposure in daily life.

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Knockout of Pannexin-1 Induces Hearing Loss

Cited by 11 publications

References 46 publications

Double deletion of Panx1 and Panx3 affects skin and bone but not hearing

Double deletion of Panx1 and Panx3 affects skin and bone but not hearing

Hearing loss is an early biomarker in APP/PS1 Alzheimer’s disease mice

Cx26 heterozygous mutations cause hyperacusis-like hearing oversensitivity and increase susceptibility to noise

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