Alox8, also known as murine Alox15b, is a lipoxygenase that catalyzes the peroxidation of arachidonic acid at carbon-8 in mice. It oxygenates polyunsaturated fatty acids in S-chirality with singular reaction specificity and is involved in the arachidonate metabolism pathway. This pathway is crucial in regulating various biological processes such as inflammation and cholesterol homeostasis [1].

In mouse models, Alox8 deficiency has been linked to multiple biological and disease-related outcomes. Alox8 knockdown in mice is associated with reduced atherosclerosis, suggesting its role in this disease [1]. Deletion of Alox8 on mouse chromosome 11B3 (homologous to human ALOX15B on chromosome 17p) leads to up-regulation of the cyclooxygenase pathway, indicated by increased prostaglandin E2 levels, contributing to B-cell malignancy [2]. Also, Alox8-deficient mice show age-dependent impaired recovery from influenza infection, with differences in cytokine levels [3]. Moreover, intermittent fasting in mice with traumatic brain injury abolishes the increase of Alox8 induced by TBI, alleviating ferroptosis-related cellular damage and cognitive impairment [4].

In conclusion, Alox8 plays important roles in regulating cholesterol homeostasis, inflammation, and recovery from infection, as well as in tumorigenesis. Mouse models with Alox8 deficiency or knockdown have significantly contributed to understanding its functions in atherosclerosis, B-cell lymphoma, influenza recovery, and traumatic brain injury-related ferroptosis and cognitive impairment.

References:

1. Palmer, Megan A, Benatzy, Yvonne, Brüne, Bernhard. 2024. Murine Alox8 versus the human ALOX15B ortholog: differences and similarities. In Pflugers Archiv : European journal of physiology, 476, 1817-1832. doi:10.1007/s00424-024-02961-w. https://pubmed.ncbi.nlm.nih.gov/38637408/

2. Qi, Lu, Pan, Xiangyu, Chen, Xuelan, Liu, Yu, Xu, Zhengmin. 2023. COX-2/PGE2 upregulation contributes to the chromosome 17p-deleted lymphoma. In Oncogenesis, 12, 5. doi:10.1038/s41389-023-00451-9. https://pubmed.ncbi.nlm.nih.gov/36750552/

3. Alfardan, Rana, Guo, Changxiong, Toth, Linda A, Nie, Daotai. 2019. Impaired Recovery from Influenza A/X-31(H3N2) Infection in Mice with 8-Lipoxygenase Deficiency. In Medical sciences (Basel, Switzerland), 7, . doi:10.3390/medsci7040060. https://pubmed.ncbi.nlm.nih.gov/31013822/

4. Yang, Qiuyun, Li, Manrui, Liu, Jinyuan, Chen, Xiameng, Liang, Weibo. 2023. Intermittent fasting ameliorates neuronal ferroptosis and cognitive impairment in mice after traumatic brain injury. In Nutrition (Burbank, Los Angeles County, Calif.), 109, 111992. doi:10.1016/j.nut.2023.111992. https://pubmed.ncbi.nlm.nih.gov/36871445/