C57BL/6NCya-Prkag2^em1/Cya

Prkag2 encodes the γ2 regulatory subunit of 5′ Adenosine Monophosphate-Activated Protein Kinase (AMPK), an enzyme crucial for modulating glucose uptake and glycolysis [3,4]. AMPK is involved in numerous metabolic pathways, regulating cellular energy homeostasis, and thus Prkag2 is of great biological importance in maintaining normal metabolic functions [3,4]. Genetic models, such as KO/CKO mouse models, could potentially be valuable in further exploring its functions.

Mutations in Prkag2 lead to Glycogen storage disease of the heart, a fetal congenital disorder known as PRKAG2 syndrome [1]. This autosomal-dominant disorder is characterized by the accumulation of glycogen in heart tissue, clinically presenting as hypertrophic cardiomyopathy [1]. The syndrome also often presents with ventricular pre-excitation, progressive conduction system disease, and may have intrafamilial phenotypical variability [2,3]. A novel heterozygous variant in Prkag2 was found in an Iranian family where a 4-year-old girl had liver problems like hepatomegaly and liver cirrhosis, expanding the mutational spectrum of the gene [1].

In conclusion, Prkag2 is essential for normal regulation of glucose metabolism-related pathways through its role in the AMPK complex. Model-based research, though not specifically detailed in the provided references regarding KO/CKO mouse models, would likely further clarify its functions. The identified mutations in Prkag2 are associated with PRKAG2 syndrome, which mainly affects the heart and potentially the liver, highlighting the gene's significance in understanding these disease conditions [1,2,3].

References:

1. Beyzaei, Zahra, Ezgu, Fatih, Geramizadeh, Bita, Alborzi, Alireza, Shojazadeh, Alireza. 2021. Novel PRKAG2 variant presenting as liver cirrhosis: report of a family with 2 cases and review of literature. In BMC medical genomics, 14, 33. doi:10.1186/s12920-021-00879-1. https://pubmed.ncbi.nlm.nih.gov/33509202/

2. Cheng, W P, Song, X W, Zhang, B L. . [Research progress of PRKAG2 cardiac syndrome]. In Zhonghua xin xue guan bing za zhi, 52, 966-972. doi:10.3760/cma.j.cn112148-20230916-00166. https://pubmed.ncbi.nlm.nih.gov/39143794/

3. Marcu, Andreea Sorina, Vătăşescu, Radu, Onciul, Sebastian, Rădoi, Viorica, Jurcuţ, Ruxandra. 2022. Intrafamilial Phenotypical Variability Linked to PRKAG2 Mutation-Family Case Report and Review of the Literature. In Life (Basel, Switzerland), 12, . doi:10.3390/life12122136. https://pubmed.ncbi.nlm.nih.gov/36556501/

4. Gollob, Michael H, Green, Martin S, Tang, Anthony S L, Roberts, Robert. . PRKAG2 cardiac syndrome: familial ventricular preexcitation, conduction system disease, and cardiac hypertrophy. In Current opinion in cardiology, 17, 229-34. doi:. https://pubmed.ncbi.nlm.nih.gov/12015471/