Nynrin-KO Mouse

Nynrin is a gene with diverse functions. It is a transcription factor that plays a crucial role in modulating mitochondrial function, especially in hematopoietic stem cells (HSCs). It is also an LTR retroelement-derived gene potentially contributing to placental emergence in therian mammals. In addition, it has been associated with various diseases, suggesting its importance in multiple biological processes [1,2].

In HSCs, knockout of Nynrin leads to a decrease in HSC frequency, dormancy, and self-renewal. This is accompanied by increased mitochondrial dysfunction, indicated by abnormal mitochondrial permeability transition pore (mPTP) opening, mitochondrial swelling, and elevated ROS levels. These changes reduce HSC radiation tolerance and promote necrosis-like phenotypes. On the contrary, Nynrin overexpression in HSCs decreases irradiation-induced lethality. The deletion of Nynrin activates Ppif, causing overexpression of cyclophilin D (CypD) and further mitochondrial dysfunction. Strategies like Ppif haploinsufficiency or pharmacological inhibition of CypD can mitigate these effects and restore HSC function in Nynrin-deficient mice [1].

In conclusion, Nynrin is a critical regulator of mitochondrial function in HSCs. The study of Nynrin knockout mouse models has revealed its significance in maintaining HSC function. Additionally, its association with placental emergence and potential roles in diseases such as Wilms tumor, melanoma, and acute myeloid leukemia suggest its importance in understanding mammalian development and disease mechanisms [1, 2, 4-6, 9].

References:

1. Zhou, Chengfang, Kuang, Mei, Tao, Yin, Wang, Junping, Hou, Yu. 2024. Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening. In Cell stem cell, 31, 1359-1375.e8. doi:10.1016/j.stem.2024.06.007. https://pubmed.ncbi.nlm.nih.gov/38955185/

2. Plianchaisuk, Arnon, Kusama, Kazuya, Kato, Kiyoko, Tamura, Kazuhiro, Iwasaki, Wataru. . Origination of LTR Retroelement-Derived NYNRIN Coincides with Therian Placental Emergence. In Molecular biology and evolution, 39, . doi:10.1093/molbev/msac176. https://pubmed.ncbi.nlm.nih.gov/35959649/