Kcnq4-KO Mouse

Kcnq4, or Potassium voltage-gated channel subfamily q member 4, is a voltage-gated potassium channel crucial for maintaining ion homeostasis and regulating hair cell membrane potential in the inner ear [1,2,3,4]. It is also involved in regulating neuronal excitability in the auditory pathway [5]. Mutations in Kcnq4 are associated with multiple forms of hearing loss, such as non-syndromic, noise-induced, and age-related hearing loss [1,2,3,7].

In Kcnq4 knockout mice, the acoustic startle reflex is exaggerated with minimal habituation, suggesting that the deletion affects both cochlear function and the excitability of startle-related neuronal networks [6]. Additionally, a mouse model harboring Kcnq4W276S/+ recapitulating DFNA2 (a form of progressive hearing loss with outer hair cell (OHC) degeneration) was used. In vivo gene editing targeting OHCs to disrupt the dominant-negative allele significantly improved auditory thresholds, demonstrating the importance of Kcnq4 in maintaining normal hearing function [8].

In conclusion, Kcnq4 is essential for normal auditory function. Studies using gene knockout and other genetic models in mice have revealed its role in hearing-related processes and have shown potential for developing targeted therapies for hearing loss associated with Kcnq4 mutations [6,8].

References:

1. Rim, John Hoon, Choi, Jae Young, Jung, Jinsei, Gee, Heon Yung. 2021. Activation of KCNQ4 as a Therapeutic Strategy to Treat Hearing Loss. In International journal of molecular sciences, 22, . doi:10.3390/ijms22052510. https://pubmed.ncbi.nlm.nih.gov/33801540/

2. Oh, Kyung Seok, Roh, Jae Won, Joo, Sun Young, Choi, Jae Young, Gee, Heon Yung. 2023. Overlooked KCNQ4 variants augment the risk of hearing loss. In Experimental & molecular medicine, 55, 844-859. doi:10.1038/s12276-023-00976-4. https://pubmed.ncbi.nlm.nih.gov/37009795/

3. Nie, Liping. . KCNQ4 mutations associated with nonsyndromic progressive sensorineural hearing loss. In Current opinion in otolaryngology & head and neck surgery, 16, 441-4. doi:10.1097/MOO.0b013e32830f4aa3. https://pubmed.ncbi.nlm.nih.gov/18797286/

4. Homma, Kazuaki. 2022. The Pathological Mechanisms of Hearing Loss Caused by KCNQ1 and KCNQ4 Variants. In Biomedicines, 10, . doi:10.3390/biomedicines10092254. https://pubmed.ncbi.nlm.nih.gov/36140355/

5. Wang, Qiong, Zhao, Guodun, Ding, Huijuan, Gao, Zhaobing, Feng, Jing. 2024. Trpv1-lineage neuron-expressing Kcnq4 channel modulates itch sensation in mice. In Pain, , . doi:10.1097/j.pain.0000000000003479. https://pubmed.ncbi.nlm.nih.gov/39560444/

6. Maamrah, Baneen, Pocsai, Krisztina, Bayasgalan, Tsogbadrakh, Csemer, Andrea, Pál, Balázs. 2023. KCNQ4 potassium channel subunit deletion leads to exaggerated acoustic startle reflex in mice. In Neuroreport, 34, 232-237. doi:10.1097/WNR.0000000000001883. https://pubmed.ncbi.nlm.nih.gov/36789839/

7. Yen, Ting-Ting, Chen, I-Chieh, Hua, Men-Wei, Chen, Yi-Ming, Jiang, Rong-San. 2021. A KCNQ4 c.546C>G Genetic Variant Associated with Late Onset Non-Syndromic Hearing Loss in a Taiwanese Population. In Genes, 12, . doi:10.3390/genes12111711. https://pubmed.ncbi.nlm.nih.gov/34828318/

8. Noh, Byunghwa, Rim, John Hoon, Gopalappa, Ramu, Kim, Hyongbum Henry, Jung, Jinsei. 2022. In vivo outer hair cell gene editing ameliorates progressive hearing loss in dominant-negative Kcnq4 murine model. In Theranostics, 12, 2465-2482. doi:10.7150/thno.67781. https://pubmed.ncbi.nlm.nih.gov/35265220/