C57BL/6JCya-Ccnd2^em1/Cya

Ccnd2, also known as Cyclin D2, is a critical cell cycle regulator and a key member of the cyclin D2-CDK4 (DC) complex. It plays a significant role in the cell cycle, specifically in the G1/S transition, and is involved in various biological processes such as cell proliferation, development, and tissue repair [2].

In aCML patients, Ccnd2 mutations in codons 280 and 281 were found in two cases, which rapidly developed progressive characteristics, suggesting it could be a new marker of aggressive disease [1]. Ccnd2 variants in the proximal region were associated with microcephaly, symmetric short stature, and mild developmental delay, while distal variants cause brain overgrowth [2]. Overexpression of Ccnd2 in human induced pluripotent stem cell-derived cardiomyocytes enhanced their efficacy for myocardial repair in swine and mouse models of myocardial infarction, leading to increased cell engraftment, improved cardiac function, and reduced infarct size [3,5,6]. In thyroid carcinoma, Ccnd2 expression was significantly increased, and along with miR-206, could potentially be biomarkers for diagnosis [4]. In cyclin D1-mantle cell lymphoma, Ccnd2 translocations were identified in a subset of cases, hijacking immunoglobulin light-chain enhancers [7].

In conclusion, Ccnd2 is crucial for cell cycle regulation and has implications in multiple biological processes and diseases. Studies, including those using animal models like mice, have revealed its role in conditions such as aCML, microcephaly-related disorders, myocardial infarction repair, thyroid carcinoma diagnosis, and mantle cell lymphoma pathogenesis. These findings enhance our understanding of the biological functions of Ccnd2 and its potential as a biomarker or therapeutic target in various diseases.

References:

1. Iaquinta, Giovanni, Scalzulli, Emilia, Angeloni, Silvia, Grammatico, Paola, Breccia, Massimo. 2023. CCND2 mutations in atypical chronic myeloid leukemia: a report of two cases. In Leukemia & lymphoma, 64, 1730-1732. doi:10.1080/10428194.2023.2232495. https://pubmed.ncbi.nlm.nih.gov/37435984/

2. Pirozzi, Filomena, Lee, Benson, Horsley, Nicole, Sanchez-Lara, Pedro A, Mirzaa, Ghayda M. 2021. Proximal variants in CCND2 associated with microcephaly, short stature, and developmental delay: A case series and review of inverse brain growth phenotypes. In American journal of medical genetics. Part A, 185, 2719-2738. doi:10.1002/ajmg.a.62362. https://pubmed.ncbi.nlm.nih.gov/34087052/

3. Zhao, Meng, Nakada, Yuji, Wei, Yuhua, Walcott, Gregory P, Zhang, Jianyi. 2021. Cyclin D2 Overexpression Enhances the Efficacy of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Myocardial Repair in a Swine Model of Myocardial Infarction. In Circulation, 144, 210-228. doi:10.1161/CIRCULATIONAHA.120.049497. https://pubmed.ncbi.nlm.nih.gov/33951921/

4. Yuan, Shifa, Liu, Zhijun, Yu, Shanshan, Wang, Xiaolei, Shi, Jian. 2023. CCND2 and miR-206 as potential biomarkers in the clinical diagnosis of thyroid carcinoma by fine-needle aspiration cytology. In World journal of surgical oncology, 21, 22. doi:10.1186/s12957-023-02899-w. https://pubmed.ncbi.nlm.nih.gov/36694220/

5. Fan, Chengming, Fast, Vladimir G, Tang, Yawen, Zhu, Wuqiang, Zhang, Jianyi. 2019. Cardiomyocytes from CCND2-overexpressing human induced-pluripotent stem cells repopulate the myocardial scar in mice: A 6-month study. In Journal of molecular and cellular cardiology, 137, 25-33. doi:10.1016/j.yjmcc.2019.09.011. https://pubmed.ncbi.nlm.nih.gov/31629738/

6. Zhu, Wuqiang, Zhao, Meng, Mattapally, Saidulu, Chen, Sifeng, Zhang, Jianyi. 2017. CCND2 Overexpression Enhances the Regenerative Potency of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Remuscularization of Injured Ventricle. In Circulation research, 122, 88-96. doi:10.1161/CIRCRESAHA.117.311504. https://pubmed.ncbi.nlm.nih.gov/29018036/

7. Martín-Garcia, David, Navarro, Alba, Valdés-Mas, Rafael, Campo, Elias, Beà, Sílvia. 2018. CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1- mantle cell lymphoma. In Blood, 133, 940-951. doi:10.1182/blood-2018-07-862151. https://pubmed.ncbi.nlm.nih.gov/30538135/