Prkacb-KO Mouse

Prkacb, encoding the protein kinase A catalytic subunit beta, functions in the protein kinase A signaling pathway. This pathway is crucial in various biological processes, and Prkacb's role in it underscores its biological importance [1].

In marsupials, Prkacb is a novel imprinted gene. There is parent-of-origin-specific DNA methylation in its differentially methylated region (DMR), with the maternal allele methylated and the paternal allele unmethylated. Paternal expression of a Prkacb lncRNA and an mRNA isoform was identified. Imprinting of Prkacb in marsupials may indicate a conserved selection pressure for imprinting of the protein kinase A signaling pathway in therians [1].

In humans, genetic variants in Prkacb have been associated with skeletal and endocrine disorders. For instance, in subjects with primary pigmented nodular adrenocortical disease (PPNAD) and related disorders, two possibly pathogenic Prkacb gene variants were identified. The p.K286del variant affected Prkacb protein stability and increased PKA signaling, potentially associated with a novel syndrome of endocrine and skeletal abnormalities [2]. Also, a somatic mutation p.S54L in Prkacb was found in a cortisol-producing adenoma (CPA) from a patient with severe Cushing syndrome. This mutation hampered type I holoenzyme formation, made the holoenzymes highly sensitive to cAMP, and at baseline drove the adenoma cells to higher cAMP signaling activity, contributing to their autonomous growth [3].

In conclusion, Prkacb is essential in the protein kinase A signaling pathway. Studies in marsupials have revealed its imprinting characteristics, while human studies have linked its genetic variants to endocrine and skeletal diseases. These findings contribute to our understanding of Prkacb's biological functions and its role in disease conditions.

References:

1. Newman, Trent, Bond, Donna M, Ishihara, Teruhito, Shaw, Geoff, Renfree, Marilyn B. 2024. PRKACB is a novel imprinted gene in marsupials. In Epigenetics & chromatin, 17, 29. doi:10.1186/s13072-024-00552-8. https://pubmed.ncbi.nlm.nih.gov/39342354/

2. Espiard, Stephanie, Drougat, Ludivine, Settas, Nikolaos, Levine, Michael A, Stratakis, Constantine A. . PRKACB variants in skeletal disease or adrenocortical hyperplasia: effects on protein kinase A. In Endocrine-related cancer, 27, 647-656. doi:10.1530/ERC-20-0309. https://pubmed.ncbi.nlm.nih.gov/33055300/

3. Espiard, Stéphanie, Knape, Matthias J, Bathon, Kerstin, Stratakis, Constantine A, Bertherat, Jérôme. 2018. Activating PRKACB somatic mutation in cortisol-producing adenomas. In JCI insight, 3, . doi:10.1172/jci.insight.98296. https://pubmed.ncbi.nlm.nih.gov/29669941/