RGD Reference Report - TALEN-mediated generation of Nkx3.1 knockout rat model. - Rat Genome Database

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TALEN-mediated generation of Nkx3.1 knockout rat model.

Authors: Lee, Ji Min  Kim, Ukjin  Yang, Hyokyung  Ryu, Bokyeong  Kim, Jin  Sakuma, Tetsushi  Yamamoto, Takashi  Park, Jae-Hak 
Citation: Lee JM, etal., Prostate. 2021 Feb;81(3):182-193. doi: 10.1002/pros.24095. Epub 2020 Dec 28.
RGD ID: 150573817
Pubmed: PMID:33368416   (View Abstract at PubMed)
DOI: DOI:10.1002/pros.24095   (Journal Full-text)


BACKGROUND: Recent developments in gene editing, using transcriptional activator-like effector nucleases (TALENs), have greatly helped the generation of genetically engineered animal models. The NK3 homeobox 1 (NKX3.1) protein plays important roles in prostate development and protein production, and functions as a tumor suppressor. Recently, NKX3.1 was shown to be associated with breast cancer in humans.
METHODS: Our aim was to create a new rat model to elucidate the functions of NKX3.1. To that end, we generated Nkx3.1 knockout rats using TALENs and analyzed their phenotype. TALEN-mediated Nkx3.1 knockout was confirmed by T7 endonuclease I (T7E1) assay and DNA sequencing. Prostate weight and fertility were evaluated in the knockout rats, besides determining the proportion of epithelial cells and messenger RNA (mRNA) expression of genes associated with carcinogenesis. Breast tumors were examined by histopathology.
RESULTS: Results suggested Nkx3.1 knockout rats have reduced fertility, decreased prostate weights, and increased epithelial cell layers. The mRNA expression of genes related to prostate carcinogenesis, namely Ar, Akt, and Pi3k, also increased. Moreover, the Nkx3.1 knockout rats often developed malignant breast tumors.
CONCLUSIONS: We, therefore, successfully created the first Nkx3.1 knockout rat model, using TALEN-mediated gene targeting, and used it to identify defects associated with Nkx3.1 deficiency, not previously observed in mice. Loss of Nkx3.1 in rats led to lower reproductive capacity, and decreased prostate weights, apart from the risk of developing breast cancer. We, thus, proposed Nkx3.1 knockout rats as reliable models for studying the role of NKX3.1 in decreased prostate weights, fertility, and breast cancer, as well as in prostate cancer.

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
abnormal copulatory plug deposition  IMP 150573817; 150573817; 150573817compared to wild typeRGD 
decreased litter size  IMP 150573817; 150573817; 150573817compared to wild typeRGD 
decreased prostate gland weight  IMP 150573817; 150573817; 150573817compared to wild typeRGD 
prostate gland epithelial hyperplasia  IMP 150573817; 150573817; 150573817; 150573817compared to wild typeRGD 
reduced male fertility  IMP 150573817; 150573817; 150573817compared to wild typeRGD 
Objects Annotated

Genes (Rattus norvegicus)
Nkx3-1  (NK3 homeobox 1)
Nkx3-1em1Pjhak  (NK3 homeobox 1; TALEN induced mutant 1, Pjhak)


Additional Information