Abca13, a member of the ATP-binding cassette subfamily A, is predicted to be the largest ABC protein, consisting of 5058 amino acids with a long N-terminal region. It is involved in cholesterol trafficking, potentially through endocytic retrograde transport in neurons [1]. Its function is likely crucial for normal neuronal development and function, and it may play a role in the pathophysiology of psychiatric disorders [1,2]. Genetic models, such as mouse models, are valuable for studying its function.

Abca13 KO mice generated using CRISPR/Cas exhibited deficits in prepulse inhibition. In primary cultures of Abca13 KO cortical neurons, vesicular cholesterol accumulation and synaptic vesicle endocytosis were impaired. Mutations in the ABCA13 gene associated with psychiatric disorders disrupted the protein's subcellular localization and impaired cholesterol trafficking [1]. In a monkey model of autism with an ABCA13 deletion, the neuronal formation in the cortex was disorganized, and the catecholaminergic, GABAergic, and serotoninergic neuronal systems were impaired [2].

In conclusion, Abca13 plays a significant role in cholesterol trafficking in neurons, which is essential for normal neuronal function. Findings from Abca13 KO mouse and monkey models suggest its involvement in the pathophysiology of psychiatric disorders like schizophrenia, bipolar disorder, major depression, and autism spectrum disorder, highlighting its importance in understanding the molecular mechanisms underlying these diseases [1,2].

References:

1. Nakato, Mitsuhiro, Shiranaga, Naoko, Tomioka, Maiko, Kioka, Noriyuki, Ueda, Kazumitsu. 2020. ABCA13 dysfunction associated with psychiatric disorders causes impaired cholesterol trafficking. In The Journal of biological chemistry, 296, 100166. doi:10.1074/jbc.RA120.015997. https://pubmed.ncbi.nlm.nih.gov/33478937/

2. Iritani, Shuji, Torii, Youta, Habuchi, Chikako, Isoda, Masaki, Ozaki, Norio. 2018. The neuropathological investigation of the brain in a monkey model of autism spectrum disorder with ABCA13 deletion. In International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, 71, 130-139. doi:10.1016/j.ijdevneu.2018.09.002. https://pubmed.ncbi.nlm.nih.gov/30201574/