Lbr, short for Lamin B receptor, is a nuclear-membrane protein with sterol reductase activity. It resides in the inner nuclear membrane, providing attachment sites for chromatin and the nuclear lamina, thus being crucial for the functional organization of the nucleus. It is also involved in regulating heterochromatin organization [1,2].

Mutations in Lbr have been linked to rare human disorders, ranging from the benign Pelger-Huet anomaly (PHA), which affects white blood cell morphology and chromatin organization, to embryonic lethality as in Greenberg dysplasia (GRBGD). A mouse model with a 236bp N-terminal deletion in the Lbr gene recapitulates human PHA phenotypes better than existing models, without disrupting X chromosome inactivation, providing a valuable pre-clinical tool [1]. Additionally, Lbr has been found to be involved in cellular processes such as senescence. Knock-down of LBR facilitated the induction of cellular senescence by excess thymidine in HeLa cells and induced it in normal human diploid fibroblast TIG-7 cells, suggesting decreased LBR function is involved in cellular senescence induction [3].

In conclusion, Lbr is essential for nuclear organization and heterochromatin regulation. Mouse models with Lbr gene modifications, like the N-terminal deletion model, have been crucial in understanding its role in diseases such as PHA. The study of Lbr in cellular senescence also provides insights into the molecular mechanisms underlying this process, contributing to our understanding of both normal biological functions and disease-associated processes.

References:

1. Young, Alexander Neil, Perlas, Emerald, Ruiz-Blanes, Nerea, Giannakouros, Thomas, Cerase, Andrea. 2021. Deletion of LBR N-terminal domains recapitulates Pelger-Huet anomaly phenotypes in mouse without disrupting X chromosome inactivation. In Communications biology, 4, 478. doi:10.1038/s42003-021-01944-2. https://pubmed.ncbi.nlm.nih.gov/33846535/

2. Chu, A, Rassadi, R, Stochaj, U. . Velcro in the nuclear envelope: LBR and LAPs. In FEBS letters, 441, 165-9. doi:. https://pubmed.ncbi.nlm.nih.gov/9883877/

3. Arai, Rumi, En, Atsuki, Takauji, Yuki, Fujii, Michihiko, Ayusawa, Dai. 2019. Lamin B receptor (LBR) is involved in the induction of cellular senescence in human cells. In Mechanisms of ageing and development, 178, 25-32. doi:10.1016/j.mad.2019.01.001. https://pubmed.ncbi.nlm.nih.gov/30615890/