Blvrb-KO Mouse

Blvrb, also known as biliverdin reductase B, is an NAD(P)H-dependent enzyme that catalyzes the reduction of biliverdin to bilirubin, playing a crucial role in maintaining cellular redox status. It is involved in redox-regulated pathways, such as those related to hematopoietic cell fate determination and the tumor necrosis factor stress pathway [1,3]. Genetic models, like mouse models, have been valuable in studying its functions.

In Blvrb-deficient mice, steady-state hematopoiesis is not affected, but an important cytoprotective function in stress hematopoiesis is revealed. There is a dichotomous megakaryocyte-biased hematopoietic recovery, with defective stress erythropoiesis in spleens and bone marrow erythroid development, accompanied by defective lipid peroxidation [1]. In humans, a loss-of-function mutation (BLVRB(S111L)) is causally associated with enhanced platelet production, highlighting its role in thrombopoiesis [2].

In conclusion, Blvrb is essential for redox-regulated hematopoietic cell fate, especially in megakaryocyte and erythroid development, as well as in stress hematopoiesis. Mouse models, particularly Blvrb-deficient mice, have provided key insights into its role in stress-related hematopoietic processes, and human studies suggest its importance in thrombopoiesis-related disorders [1,2].

References:

1. Nesbitt, Natasha M, Malone, Lisa E, Liu, Zhaoyan, Zhu, Wei, Bahou, Wadie F. 2020. Divergent erythroid megakaryocyte fates in Blvrb-deficient mice establish non-overlapping cytoprotective functions during stress hematopoiesis. In Free radical biology & medicine, 164, 164-174. doi:10.1016/j.freeradbiomed.2020.12.015. https://pubmed.ncbi.nlm.nih.gov/33359909/

2. Wu, Song, Li, Zongdong, Gnatenko, Dmitri V, Nesbitt, Natasha M, Bahou, Wadie F. 2016. BLVRB redox mutation defines heme degradation in a metabolic pathway of enhanced thrombopoiesis in humans. In Blood, 128, 699-709. doi:10.1182/blood-2016-02-696997. https://pubmed.ncbi.nlm.nih.gov/27207795/

3. Bahou, Wadie F, Marchenko, Natalia, Nesbitt, Natasha M. 2023. Metabolic Functions of Biliverdin IXβ Reductase in Redox-Regulated Hematopoietic Cell Fate. In Antioxidants (Basel, Switzerland), 12, . doi:10.3390/antiox12051058. https://pubmed.ncbi.nlm.nih.gov/37237924/