Prkra-KO Mouse

Prkra, encoding PACT (protein activator of interferon-induced double-stranded RNA-activated protein kinase PKR), is involved in multiple cellular pathways. It has a well-characterized role as a PKR activator during the integrated stress response (ISR) [1,3]. Mutations in Prkra are associated with DYT-PRKRA (dystonia 16), and it also has implications in embryonic external ear development, cancer progression, and chemoresistance [1-6]. Mouse models are valuable for studying Prkra's function.

In DYT-PRKRA, the P222L mutation in Prkra enhances PACT's ability to induce IFN-β and increases the basal expression of IFN-β and IFN-stimulated genes, offering insights into the molecular pathomechanisms [1]. In the Prkra short-ear mouse model, point mutations in Prkra alter mRNA, lncRNA, and miRNA expression during embryonic external ear development, suggesting a role in regulating external ear development [2,6,7]. In pancreatic cancer, PRKRA promotes cancer progression by upregulating MMP1 transcription via the NF-κB pathway, and in mucinous ovarian cancer, PRKRA/PACT expression promotes chemoresistance [4,5].

In conclusion, Prkra plays crucial roles in multiple biological processes and disease conditions. Mouse models, especially those with Prkra mutations, have been instrumental in uncovering its functions in diseases like DYT-PRKRA, embryonic external ear development, and cancer, providing potential therapeutic targets for these diseases.

References:

1. Vaughn, Lauren S, Frederick, Kenneth, Burnett, Samuel B, Cardoso, Francisco, Patel, Rekha C. 2022. DYT-PRKRA Mutation P222L Enhances PACT's Stimulatory Activity on Type I Interferon Induction. In Biomolecules, 12, . doi:10.3390/biom12050713. https://pubmed.ncbi.nlm.nih.gov/35625640/

2. Liu, Wei, Lin, Lin, Yang, Qinghua, Jin, Shengyang, Jiang, Haiyue. 2023. Prkra Mutation Alters mRNA Expression During Embryonic External Ear Development. In The Journal of craniofacial surgery, 34, e387-e391. doi:10.1097/SCS.0000000000009318. https://pubmed.ncbi.nlm.nih.gov/37185168/

3. Frederick, Kenneth, Patel, Rekha C. 2023. Luteolin protects DYT-PRKRA cells from apoptosis by suppressing PKR activation. In Frontiers in pharmacology, 14, 1118725. doi:10.3389/fphar.2023.1118725. https://pubmed.ncbi.nlm.nih.gov/36874028/

4. Qiu, Jiangdong, Feng, Mengyu, Yang, Gang, Luo, Wenhao, Zhang, Taiping. 2023. PRKRA promotes pancreatic cancer progression by upregulating MMP1 transcription via the NF-κB pathway. In Heliyon, 9, e17194. doi:10.1016/j.heliyon.2023.e17194. https://pubmed.ncbi.nlm.nih.gov/37484321/

5. Hisamatsu, Takeshi, McGuire, Michael, Wu, Sherry Y, Lopez-Berestein, Gabriel, Sood, Anil K. 2018. PRKRA/PACT Expression Promotes Chemoresistance of Mucinous Ovarian Cancer. In Molecular cancer therapeutics, 18, 162-172. doi:10.1158/1535-7163.MCT-17-1050. https://pubmed.ncbi.nlm.nih.gov/30305341/

6. Liu, Wei, Jin, Shengyang, Lin, Lin, Yang, Qinghua, Jiang, Haiyue. 2022. Prkra Mutation Alters Long Noncoding RNA Expression During Embryonic External Ear Development. In The Journal of craniofacial surgery, 34, e156-e161. doi:10.1097/SCS.0000000000008909. https://pubmed.ncbi.nlm.nih.gov/35968982/

7. Liu, Wei, Lin, Lin, Yang, Qinghua, Jin, Shengyang, Jiang, Haiyue. 2022. Point Mutation in Prkra Alters miRNA Expression During Embryonic External Ear Development. In The Journal of craniofacial surgery, 34, 777-784. doi:10.1097/SCS.0000000000008837. https://pubmed.ncbi.nlm.nih.gov/35968958/