Osbpl2-KO Mouse

Osbpl2, also known as oxysterol-binding protein-related protein 2, is an important regulator in cellular lipid metabolism and transport. It is involved in maintaining lipid homeostasis, and has been implicated in pathways related to cholesterol biosynthesis, such as the AMPK signaling pathway. Additionally, it may play a role in autophagy, ciliogenesis, and the Sonic Hedgehog (Shh) signaling pathway, which are crucial for normal physiological functions [1,2,3,5,6]. Animal models, especially gene-knockout (KO) models, have been valuable in understanding its functions.

Osbpl2-KO mice exhibited progressive hearing loss, abnormal cochlear development with defective cilia, and disrupted endolysosomal homeostasis and autophagy [1,3]. In Osbpl2-disrupted pigs, there was progressive hearing loss along with hypercholesterolaemia, indicating a potential link between auditory dysfunction and dyslipidaemia [2]. In cell-based studies, knockdown of Osbpl2 led to increased cholesterol and cholesteryl ester accumulation by upregulating SQLE expression via the AMPK/SP1 and SREBF2 signalling pathways [5]. In the context of age-related hearing loss, inhibition of Osbpl2 in hair cell-like inner ear cells led to apoptosis through inactivation of the AKT/FOXG1 signaling pathway [4].

In conclusion, Osbpl2 is essential for normal auditory function, lipid metabolism, and cellular homeostasis. The use of KO mouse and other animal models has significantly contributed to understanding its role in non-syndromic hearing loss, hypercholesterolaemia, and other related disease conditions, providing insights into potential therapeutic strategies for these disorders.