Atrn, encoding Attractin, is a widely expressed member of the cell adhesion and guidance protein family. It is closely related to cellular immunity, neurodevelopment, and energy homeostasis [2,6]. Atrn may be involved in regulating mitochondrial function, and it plays a role in central myelination and embryonic development, such as regulating zebrafish epiboly [1,3,4].

In genetic models, Atrn null mutant mice display a pleiotropic phenotype including dark fur, juvenile-onset spongiform neurodegeneration, hypomyelination, tremor, reduced body weight and adiposity [5]. ATRN-G505C(KI/KI) rats show impaired working memory in the water maze, potentially due to reduced myelin basic protein (MBP) expression [2]. In zebrafish, atrn knockout leads to more pronounced attack behavior and elevated testosterone levels [6]. Homozygous mutation in the ATRN gene in humans is associated with hypomyelinating leukodystrophy [3].

In summary, Atrn is crucial for multiple biological processes, especially in neurodevelopment and myelination. Findings from gene knockout models in mice, rats, and zebrafish have revealed its significant roles in neurodegenerative diseases, working memory, and behavioral phenotypes related to testosterone levels. These models contribute to understanding the molecular mechanisms underlying these disease-related conditions [2,3,5,6].

References:

1. Sun, Qingrui, Liu, Xingfeng, Gong, Bo, Meng, Anming, Jia, Shunji. 2017. Alkbh4 and Atrn Act Maternally to Regulate Zebrafish Epiboly. In International journal of biological sciences, 13, 1051-1066. doi:10.7150/ijbs.19203. https://pubmed.ncbi.nlm.nih.gov/28924386/

2. Liu, Meng-Qi, Xue, Cheng, Li, Xiao-Hui, Xu, Xi-Jia, Zhang, Wei-Ning. 2023. Mutation of the attractin gene impairs working memory in rats. In Brain and behavior, 13, e2876. doi:10.1002/brb3.2876. https://pubmed.ncbi.nlm.nih.gov/36621889/

3. Shahrour, Maher Awni, Ashhab, Motee, Edvardson, Simon, Abu-Libdeh, Bassam, Elpeleg, Orly. 2017. Hypomyelinating leukodystrophy associated with a deleterious mutation in the ATRN gene. In Neurogenetics, 18, 135-139. doi:10.1007/s10048-017-0515-7. https://pubmed.ncbi.nlm.nih.gov/28493104/

4. Paz, Jeff, Yao, Honghong, Lim, Hyo Sook, Lu, Xin-Yun, Zhang, Wei. 2006. The neuroprotective role of attractin in neurodegeneration. In Neurobiology of aging, 28, 1446-56. doi:. https://pubmed.ncbi.nlm.nih.gov/16860906/

5. Walker, Will P, Aradhya, Swaroop, Hu, Che-Lin, Barsh, Gregory S, Gunn, Teresa M. . Genetic analysis of attractin homologs. In Genesis (New York, N.Y. : 2000), 45, 744-56. doi:. https://pubmed.ncbi.nlm.nih.gov/18064672/

6. Li, Nan, Gao, Shuzhan, Wang, Shuang, Xu, Xijia, Zhao, Qingshun. 2021. Attractin Participates in Schizophrenia by Affecting Testosterone Levels. In Frontiers in cell and developmental biology, 9, 755165. doi:10.3389/fcell.2021.755165. https://pubmed.ncbi.nlm.nih.gov/34869343/