Cry2-KO Mouse

Cry2, or Cryptochrome 2, is a gene encoding a protein that plays diverse and crucial roles. In plants, it serves as a blue-light photoreceptor regulating various growth aspects, and in mammals, it is a core circadian clock regulator. In the plant circadian clock, it represses CLOCK/BMAL1-induced transcription activation, while in mammals, it is related to DNA-repair enzymes and modulates transcriptional response to DNA damage. It is involved in pathways like photomorphogenesis in plants, and in mammals, it impacts processes related to cell growth, adipogenesis, and circadian-related functions [1,2,3,4,5,6,7].

In Arabidopsis, loss-of-function studies showed that CRY2 suppresses cell division in the root apical meristem to downregulate root elongation in darkness, and blue-light oligomerizes CRY2 to de-repress root elongation [1]. In adipogenesis, disruption of the interaction between Cry2 and Per2 through a C432 mutation in Cry2 led to loss of repression of clock transcription activation and suppressed adipocyte differentiation, indicating Cry2 promotes adipogenesis via this interaction [6,7]. In 5xFAD mice, down-regulation of CRY2 attenuated the sleep-deprivation-induced cognitive decline, suggesting CRY2 mediates this cognitive decline [8]. In recurrent spontaneous abortion, knockdown of CRY2 in HTR-8/SVneo cells promoted trophoblast migration and invasion, while overexpression had the opposite effect, as CRY2 inhibits the c-Myc-BMAL1-MMP2/9 pathway [9].

In conclusion, Cry2 is essential for regulating plant growth, adipogenesis, cognitive function, and trophoblast behavior. Studies using gene-knockout or mutation models in plants and mice have revealed its role in these biological processes. In the context of diseases, understanding Cry2 function may offer insights into treating conditions like cognitive decline and recurrent spontaneous abortion.

References:

1. Zeng, Desheng, Lv, Junqing, Li, Xu, Liu, Hongtao. 2024. The Arabidopsis blue-light photoreceptor CRY2 is active in darkness to inhibit root growth. In Cell, 188, 60-76.e20. doi:10.1016/j.cell.2024.10.031. https://pubmed.ncbi.nlm.nih.gov/39549699/

2. Jiang, Bochen, Zhong, Zhenhui, Gu, Lianfeng, Wang, Xu, Lin, Chentao. 2023. Light-induced LLPS of the CRY2/SPA1/FIO1 complex regulating mRNA methylation and chlorophyll homeostasis in Arabidopsis. In Nature plants, 9, 2042-2058. doi:10.1038/s41477-023-01580-0. https://pubmed.ncbi.nlm.nih.gov/38066290/

3. Li, Youping, Shi, Yiting, Li, Minze, Liu, Hongtao, Yang, Shuhua. . The CRY2-COP1-HY5-BBX7/8 module regulates blue light-dependent cold acclimation in Arabidopsis. In The Plant cell, 33, 3555-3573. doi:10.1093/plcell/koab215. https://pubmed.ncbi.nlm.nih.gov/34427646/

4. Miller, Simon, Kesherwani, Manish, Chan, Priscilla, Kay, Steve A, Hirota, Tsuyoshi. 2022. CRY2 isoform selectivity of a circadian clock modulator with antiglioblastoma efficacy. In Proceedings of the National Academy of Sciences of the United States of America, 119, e2203936119. doi:10.1073/pnas.2203936119. https://pubmed.ncbi.nlm.nih.gov/36161947/

5. Chan, Alanna B, Parico, Gian Carlo G, Fribourgh, Jennifer L, Partch, Carrie L, Lamia, Katja A. . CRY2 missense mutations suppress P53 and enhance cell growth. In Proceedings of the National Academy of Sciences of the United States of America, 118, . doi:10.1073/pnas.2101416118. https://pubmed.ncbi.nlm.nih.gov/34183418/

6. Li, Weini, Xiong, Xuekai, Kiperman, Tali, Ma, Ke. 2023. Transcription repression of Cry2 via Per2 interaction promotes adipogenesis. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.03.12.532323. https://pubmed.ncbi.nlm.nih.gov/36993226/

7. Li, Weini, Xiong, Xuekai, Kiperman, Tali, Ma, Ke. 2023. Transcription Repression of CRY2 via PER2 Interaction Promotes Adipogenesis. In Molecular and cellular biology, 43, 500-514. doi:10.1080/10985549.2023.2253710. https://pubmed.ncbi.nlm.nih.gov/37724597/

8. Luo, Sumei, Guo, Lizhe, Chen, Na, Wang, Yunjiao, Wang, E. 2024. CRY2 mediates the cognitive decline induced by sleep deprivation in 5xFAD mice. In PloS one, 19, e0306930. doi:10.1371/journal.pone.0306930. https://pubmed.ncbi.nlm.nih.gov/39012854/

9. Wu, Lianzhi, Cheng, Biheng, Liu, Qian, Jiang, Ping, Yang, Jing. . CRY2 suppresses trophoblast migration and invasion in recurrent spontaneous abortion. In Journal of biochemistry, 167, 79-87. doi:10.1093/jb/mvz076. https://pubmed.ncbi.nlm.nih.gov/31536114/