Crym-KO Mouse

Crym, encoding μ -crystallin, is an important gene with multiple functions. It codes for a NADPH -regulated thyroid hormone binding protein, which buffers the amount of freely available triiodothyronine (T3) in the cytosol, thus controlling thyroid hormone action. It is also involved in the lysine degradation pathway as a ketimine reductase when not bound to thyroid hormone [2,4]. The gene is expressed in various tissues like the brain, muscle, prostate, and kidney, and is associated with multiple biological processes and diseases [4]. Genetic models, especially knockout mouse models, are valuable for studying its functions.

In adult mice, CRISPR -Cas9 -mediated knockout of Crym in striatal astrocytes led to perseverative behaviours, increased fast synaptic excitation in medium spiny neurons, and a dysfunctional excitatory-inhibitory synaptic balance. This revealed that Crym -positive striatal astrocytes gate perseveration phenotypes related to neuropsychiatric disorders [1]. In another study, liver -specific knockdown of Crym in adult mice abolished the protective effects of early-life exercise on anti-inflammatory immunity, suggesting that Crym in the liver is involved in this process [3]. Also, Crym -knockout mice showed a significant hypertrophy of fast-twitch glycolytic type IIb fibers, leading to an increase in grip strength and high-intensity running ability, indicating its role in muscle plasticity [5].

In summary, Crym is crucial for various biological functions including neural circuit regulation, anti-inflammatory immunity, and muscle function. Findings from Crym knockout mouse models have enhanced our understanding of its role in neuropsychiatric disorders, immune regulation, and muscle-related conditions, providing potential therapeutic targets for these diseases.

References:

1. Ollivier, Matthias, Soto, Joselyn S, Linker, Kay E, Wohlschlegel, James A, Khakh, Baljit S. 2024. Crym-positive striatal astrocytes gate perseverative behaviour. In Nature, 627, 358-366. doi:10.1038/s41586-024-07138-0. https://pubmed.ncbi.nlm.nih.gov/38418885/

2. Aksoy, Osman, Hantusch, Brigitte, Kenner, Lukas. 2022. Emerging role of T3-binding protein μ-crystallin (CRYM) in health and disease. In Trends in endocrinology and metabolism: TEM, 33, 804-816. doi:10.1016/j.tem.2022.09.003. https://pubmed.ncbi.nlm.nih.gov/36344381/

3. Zhang, Nini, Wang, Xinpei, Feng, Mengya, Li, Jia, Gao, Feng. 2024. Early-life exercise induces immunometabolic epigenetic modification enhancing anti-inflammatory immunity in middle-aged male mice. In Nature communications, 15, 3103. doi:10.1038/s41467-024-47458-3. https://pubmed.ncbi.nlm.nih.gov/38600123/

4. Kinney, Christian J, Bloch, Robert J. 2021. µ-Crystallin: A thyroid hormone binding protein. In Endocrine regulations, 55, 89-102. doi:10.2478/enr-2021-0011. https://pubmed.ncbi.nlm.nih.gov/34020530/

5. Seko, Daiki, Ogawa, Shizuka, Li, Tao-Sheng, Taimura, Akihiro, Ono, Yusuke. 2015. μ-Crystallin controls muscle function through thyroid hormone action. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 30, 1733-40. doi:10.1096/fj.15-280933. https://pubmed.ncbi.nlm.nih.gov/26718889/