Mice with NOP2/sun RNA methyltransferase 5 deficiency die before reaching puberty due to fatal kidney damage

Abstract

Background

NOP2/Sun RNA methyltransferase 5 (NSUN5) is an RNA methyltransferase that has a broad distribution and plays critical roles in various biological processes. However, our knowledge of the biological functions of NSUN5 in mammals is very limited. Therefore, in this study, we investigate the role of NSUN5 in mice.

Methods

In the present research, we built a mouse model (Nsun5^-/-) using the CRISPR/Cas9 system to investigated the specific role of NSUN5.

Results

We observed that Nsun5^-/- mice had a reduced body weight compared to wild-type mice. Additionally, their survival rate gradually decreased to 20% after postnatal day (PD) 21. Further examination revealed the Nsun5^-/- mice had multiple organ damage, with the most severe damage occurring in the kidneys. Moreover, we observed glycogen deposition and fibrosis, along with a notable shorting of the primary foot processes of glomeruli in Nsun5^-/- kidneys. Furthermore, we found that the kidneys of Nsun5^-/- mice showed increased expression of the apoptotic signal Caspase-3 and accumulated stronger DNA damage at PD 21.

Conclusions

In our study, we found that mice lacking NSUN5 died before puberty due to kidney fatal damage caused by DNA damage and cell apoptosis. These results suggest that NSUN5 plays a vital role in preventing the accumulation of DNA damage and cell apoptosis in the kidney.

Keywords:

• Apoptosis
• DNA damage
• kidney
• NSUN5
• RNA methyltransferases

Ethical approval

All animal experiments were carried out in compliance with the Guidelines for the Care and Use of Laboratory Animals of Shandong Normal University and were authorized by the Animal Ethics Committee of Shandong Normal University.

Informed consent statement

Not applicable.

Authors’ contributions

CZ and HYZ conceived and designed the study. HYZ performed the experiments and drafted the manuscript. XHL acquired and analyzed data. CZ and HYZ revised the manuscript. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

This manuscript contains all of the data produced during this research.

Additional information

Funding

This study was supported by the National Key R&D Program of China (2019YFA0802600) and the National Natural Science Foundation of China (32170863 and 31871512) awarded to C.Z. Support was also received from grants provided by the Shanghai Commission of Science and Technology (20DZ2270900) and the Open Project of Shandong Provincial Key Laboratory of Reproductive Medicine (SDKL2017018).