Gabbr1, encoding the γ-aminobutyric acid (GABA) type B receptor subunit 1, is crucial for prolonged neuronal inhibition in the central nervous system as GABAB receptors are obligatory heterodimers composed of subunits encoded by GABBR1 and GABBR2. It is also involved in the regulation of hematopoietic stem/progenitor cells (HSPCs) proliferation and function [1,2].

Constitutive Gabbr1-knockout mouse models have shown that Gabbr1-null HSPCs have reduced numbers in the bone marrow, diminished capacity to reconstitute irradiated recipients, and are less proliferative under steady-state and stress conditions. In vitro, Gabbr1-null HSPCs have significant defects in differentiation and expansion of the B-cell lineage [2]. In addition, monoallelic de novo non-synonymous variants in GABBR1 in humans are associated with motor and/or language delay, epilepsy, and other neurodevelopmental phenotypes, likely due to an imbalance in the excitation/inhibition balance in the central nervous system [1].

In summary, Gabbr1 plays essential roles in both the nervous and hematopoietic systems. Gene knockout mouse models have been instrumental in revealing its role in HSPC regulation, and human genetic studies have linked its variants to neurodevelopmental disorders, highlighting its significance in understanding normal biological processes and disease mechanisms.

References:

1. Cediel, Maria Lucia, Stawarski, Michal, Blanc, Xavier, Bettler, Bernhard, Antonarakis, Stylianos E. 2022. GABBR1 monoallelic de novo variants linked to neurodevelopmental delay and epilepsy. In American journal of human genetics, 109, 1885-1893. doi:10.1016/j.ajhg.2022.08.010. https://pubmed.ncbi.nlm.nih.gov/36103875/

2. Shao, Lijian, Elujoba-Bridenstine, Adedamola, Zink, Katherine E, Pajcini, Kostandin V, Tamplin, Owen J. . The neurotransmitter receptor Gabbr1 regulates proliferation and function of hematopoietic stem and progenitor cells. In Blood, 137, 775-787. doi:10.1182/blood.2019004415. https://pubmed.ncbi.nlm.nih.gov/32881992/