Adra1b-KO Mouse

Adra1b, the gene encoding the alpha-1b adrenergic receptor, is involved in the adrenergic signaling pathway. These receptors contribute to vasoconstriction in humans and are widely distributed in the peripheral and central nervous systems, playing important roles in regulating various physiological functions [3,5]. Genetic models, such as gene-knockout (KO) mouse models, are valuable tools for studying its function.

A KO mouse model with tissue-specific deletion of Adra1b in hepatocytes was generated to study its role in metabolism. Selective deletion of Adra1b in mouse liver had limited metabolic impact in lean mice. However, in female mice, loss of Adra1b in hepatocytes exacerbated diet-induced obesity, insulin resistance, and glucose intolerance, accompanied by reduced hepatic gluconeogenic capacity and adipose tissue reprogramming. This highlights the sex-dependent role of Adra1b in the sympathetic nervous system's regulation of energy and glucose homeostasis [2].

In conclusion, Adra1b plays a crucial role in vasoconstriction and is involved in the regulation of energy and glucose homeostasis, especially in female mice as revealed by the KO mouse model. Its study also has implications in understanding diseases like psoriasis, gastric cancer, and ADHD, where its gene variants or expression levels are associated with disease susceptibility or progression [1,4,6,7].

References:

1. Fan, Xing, Wang, Hongyan, Sun, Liangdan, Zhang, Xuejun, Schork, Nicholas J. 2019. Fine mapping and subphenotyping implicates ADRA1B gene variants in psoriasis susceptibility in a Chinese population. In Epigenomics, 11, 455-467. doi:10.2217/epi-2018-0131. https://pubmed.ncbi.nlm.nih.gov/30785334/

2. Silva, Anisia, Mouchiroud, Mathilde, Lavoie, Olivier, Elmquist, Joel K, Caron, Alexandre. 2024. Liver adrenoceptor alpha-1b plays a key role in energy and glucose homeostasis in female mice. In American journal of physiology. Endocrinology and metabolism, 327, E626-E635. doi:10.1152/ajpendo.00153.2024. https://pubmed.ncbi.nlm.nih.gov/39259165/

3. Adefurin, A, Ghimire, L V, Kohli, U, Stein, C M, Kurnik, D. 2016. Genetic variation in the alpha1B-adrenergic receptor and vascular response. In The pharmacogenomics journal, 17, 366-371. doi:10.1038/tpj.2016.29. https://pubmed.ncbi.nlm.nih.gov/27089938/

4. Noda, H, Miyaji, Y, Nakanishi, A, Konishi, F, Miki, Y. . Frequent reduced expression of alpha-1B-adrenergic receptor caused by aberrant promoter methylation in gastric cancers. In British journal of cancer, 96, 383-90. doi:. https://pubmed.ncbi.nlm.nih.gov/17242706/

5. Masukawa, Daiki, Takahagi, Ryo, Nakao, Yuka, Goshima, Yoshio. . L-DOPA Receptor GPR143 Functionally Couples with Adrenergic α1B Receptor at the Second Transmembrane Interface. In Biological & pharmaceutical bulletin, 46, 869-873. doi:10.1248/bpb.b23-00217. https://pubmed.ncbi.nlm.nih.gov/37394637/

6. Hawi, Ziarih, Matthews, Natasha, Barry, Edwina, Gill, Michael, Bellgrove, Mark A. 2012. A high density linkage disequilibrium mapping in 14 noradrenergic genes: evidence of association between SLC6A2, ADRA1B and ADHD. In Psychopharmacology, 225, 895-902. doi:10.1007/s00213-012-2875-x. https://pubmed.ncbi.nlm.nih.gov/23052569/

7. Wang, Tingan, Qin, Yuzhou, Lai, Hao, Huang, Mingwei, Chen, Jiansi. 2019. The prognostic value of ADRA1 subfamily genes in gastric carcinoma. In Oncology letters, 18, 3150-3158. doi:10.3892/ol.2019.10660. https://pubmed.ncbi.nlm.nih.gov/31452791/