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TALEN-mediated generation of Nkx3.1 knockout rat model.
Ji Min Lee1, Ukjin Kim1, Hyokyung Yang1
1Department of Laboratory Animal Medicine, Research Institute for Veterinary Science, BK21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
The Prostate
|December 28, 2020
Summary
We created the first Nkx3.1 knockout rat model using TALEN gene editing. This model reveals Nkx3.1 deficiency causes reduced fertility, prostate issues, and increased breast cancer risk.
Area of Science:
- Genetics and Genomics
- Animal Models
- Cancer Biology
Background:
- Transcriptional activator-like effector nucleases (TALENs) are key for genetically engineered animal models.
- NK3 homeobox 1 (NKX3.1) protein is crucial for prostate development and acts as a tumor suppressor.
- NKX3.1 is implicated in human breast cancer development.
Purpose of the Study:
- To establish a novel rat model for studying NKX3.1 functions.
- To investigate the phenotypic consequences of Nkx3.1 deficiency in rats.
Main Methods:
- Generated Nkx3.1 knockout rats using TALEN technology.
- Confirmed gene knockout via T7 endonuclease I assay and DNA sequencing.
- Assessed prostate weight, fertility, epithelial cell proportion, gene expression (Ar, Akt, Pi3k), and breast tumor histopathology.
Main Results:
- Nkx3.1 knockout rats exhibited reduced fertility and prostate weights.
- Increased epithelial cell layers and elevated mRNA expression of prostate carcinogenesis-related genes (Ar, Akt, Pi3k) were observed.
- Malignant breast tumors frequently developed in Nkx3.1 knockout rats.
Conclusions:
- Successfully developed the first Nkx3.1 knockout rat model.
- Identified novel defects associated with Nkx3.1 deficiency, including impaired reproductive capacity, decreased prostate weight, and predisposition to breast cancer.
- Proposed Nkx3.1 knockout rats as valuable models for studying NKX3.1's role in prostate and breast cancer.
