Cellular Retinoic Acid Binding Protein 1 (CRABP1) is a mediator of non-canonical activities of retinoic acid (RA). It functions by forming complexes with specific signaling molecules to regulate pathways such as MAPK and CaMKII, which are crucial for stem cell proliferation, adipocyte health, neuro-immune regulation, and heart and motor neuron function [1]. Genetic models like the Crabp1 knockout (CKO) mouse are valuable for studying its functions.

Crabp1 knockout (CKO) mice have provided significant insights. They exhibit an adult-onset ALS-like phenotype with deteriorated neuromuscular junctions, suggesting CRABP1's role in maintaining the neuromuscular junction through the CRABP1-CaMKII-Agrn signaling pathway [3]. CKO mice also show altered exosome profiles, uncovering a novel function of CRABP1 in modulating exosome secretion [2]. Additionally, CKO mice display reduced anxiety-like behaviors, lowered stress-induced corticosterone levels, and increased sensitivity of feedback inhibition in the hypothalamic-pituitary-adrenal (HPA) axis, indicating CRABP1's role in HPA axis homeostasis by modulating FKBP5 expression [4]. Ablation of ARCCRABP1 neurons (neurons expressing CRABP1 in the arcuate nucleus) in mice leads to obesity and a diabetic phenotype, highlighting the role of these neurons in energy homeostasis regulation [5]. CKO mice also have elevated basal CaMKII phosphorylation, making them more susceptible to isoproterenol-induced acute and chronic cardiac injury, showing CRABP1's protective role in the heart [6].

In conclusion, model-based research, especially using CKO mouse models, has revealed that CRABP1 is essential for multiple biological processes. It plays a protective role in diseases related to the neuromuscular junction, heart, and in stress-related disorders. The study of CRABP1 provides potential therapeutic strategies for these diseases by targeting this gene [1,3,4,6].

References:

1. Nhieu, Jennifer, Lin, Yu-Lung, Wei, Li-Na. 2022. CRABP1 in Non-Canonical Activities of Retinoic Acid in Health and Diseases. In Nutrients, 14, . doi:10.3390/nu14071528. https://pubmed.ncbi.nlm.nih.gov/35406141/

2. Nhieu, Jennifer, Wei, Chin-Wen, Ludwig, Megan, Drake, Justin M, Wei, Li-Na. 2024. CRABP1-complexes in exosome secretion. In Cell communication and signaling : CCS, 22, 381. doi:10.1186/s12964-024-01749-w. https://pubmed.ncbi.nlm.nih.gov/39075476/

3. Lin, Yu-Lung, Nhieu, Jennifer, Liu, Pei-Yao, Lowe, Dawn, Wei, Li-Na. 2022. CRABP1-CaMKII-Agrn regulates the maintenance of neuromuscular junction in spinal motor neuron. In Cell death and differentiation, 29, 1744-1756. doi:10.1038/s41418-022-00959-4. https://pubmed.ncbi.nlm.nih.gov/35217789/

4. Lin, Yu-Lung, Wei, Chin-Wen, Lerdall, Thomas A, Nhieu, Jennifer, Wei, Li-Na. 2021. Crabp1 Modulates HPA Axis Homeostasis and Anxiety-like Behaviors by Altering FKBP5 Expression. In International journal of molecular sciences, 22, . doi:10.3390/ijms222212240. https://pubmed.ncbi.nlm.nih.gov/34830120/

5. Yan, Lihong, Zhang, Xin, Jin, Liling, Liu, An, Li, Juxue. 2025. The ARCCRABP1 neurons play a crucial role in the regulation of energy homeostasis. In Nature communications, 16, 2319. doi:10.1038/s41467-025-57411-7. https://pubmed.ncbi.nlm.nih.gov/40057489/

6. Park, Sung Wook, Persaud, Shawna D, Ogokeh, Stanislas, Townsend, DeWayne, Wei, Li-Na. 2018. CRABP1 protects the heart from isoproterenol-induced acute and chronic remodeling. In The Journal of endocrinology, 236, 151-165. doi:10.1530/JOE-17-0613. https://pubmed.ncbi.nlm.nih.gov/29371236/