AU040320, also known as KIAA0319L and AAV receptor (AAVR), is a type I transmembrane protein. It is crucial for adeno-associated virus (AAV) infection as it directly binds to AAV particles, enabling AAV entry into cells. In addition, it is involved in the normal formation of proacrosomal vesicles in spermatozoa and may be related to auditory function [1,2,3].

Gene knockout (KO) mouse models have been instrumental in revealing its functions. Au040320(-/-) mice are highly resistant to AAV infection, indicating its essential role in AAV-mediated gene delivery in vivo [1]. Homozygous male KO mice for AU040320 are infertile with a globozoospermia-like phenotype due to disrupted acrosome biogenesis [2]. Moreover, AU040320-KO mice display suprathreshold deficits in wave III amplitude in auditory brainstem responses, suggesting disruption of firing and/or synchrony of activity in the auditory brainstem [3]. In sensory hair cells, AAVR knockout inhibits AAV transduction, while its conditional overexpression restores AAV transduction efficiency [4].

In conclusion, AU040320 is essential for AAV infection, acrosome biogenesis in spermatozoa, and auditory function. The use of KO mouse models has provided valuable insights into its role in these biological processes and potential implications in diseases related to AAV-based therapies, infertility, and auditory disorders.

References:

1. Pillay, S, Meyer, N L, Puschnik, A S, Chapman, M S, Carette, J E. 2016. An essential receptor for adeno-associated virus infection. In Nature, 530, 108-12. doi:10.1038/nature16465. https://pubmed.ncbi.nlm.nih.gov/26814968/

2. Guidi, Luiz G, Holloway, Zoe G, Arnoult, Christophe, Molnár, Zoltán, Velayos-Baeza, Antonio. 2018. AU040320 deficiency leads to disruption of acrosome biogenesis and infertility in homozygous mutant mice. In Scientific reports, 8, 10379. doi:10.1038/s41598-018-28666-6. https://pubmed.ncbi.nlm.nih.gov/29991750/

3. Guidi, Luiz G, Mattley, Jane, Martinez-Garay, Isabel, Velayos-Baeza, Antonio, Molnár, Zoltán. . Knockout Mice for Dyslexia Susceptibility Gene Homologs KIAA0319 and KIAA0319L have Unaffected Neuronal Migration but Display Abnormal Auditory Processing. In Cerebral cortex (New York, N.Y. : 1991), 27, 5831-5845. doi:10.1093/cercor/bhx269. https://pubmed.ncbi.nlm.nih.gov/29045729/

4. Wu, Fan, Chen, Guisheng, Hu, Rui, Sha, Suhua, Zheng, Yiqing. 2025. AAVR Expression is Essential for AAV Vector Transduction in Sensory Hair Cells. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), , e2408873. doi:10.1002/advs.202408873. https://pubmed.ncbi.nlm.nih.gov/39776318/