Hbs1l, encoding HBS1-like translational GTPase, is a crucial component in the cell's translational quality control pathways [1]. It is essential for ribosomal rescue, playing a significant role in maintaining normal cellular function and is involved in processes like erythropoiesis [2,3,4]. Genetic models, such as mouse models, have been instrumental in studying its function.

In a mouse model with a knockdown mutation in the murine Hbs1l gene (Hbs1lKO), phenotypes similar to those in Hbs1L-deficient humans were observed, including facial dysmorphism, growth restriction, and retinal deposits [1]. Hbs1ltm1a/tm1a hypomorph mice exhibited profound thinning of the entire retina, especially the outer photoreceptor layer, due to extensive photoreceptor cell apoptosis, indicating Hbs1l's role in maintaining retinal health, particularly in photoreceptor cells [2,5]. Additionally, in β0-thalassemia/HbE erythroid cells, knockdown of HBS1L using shRNA led to an upregulation of γ-globin mRNA and an increase in the percentage of fetal hemoglobin, suggesting its potential in therapeutic approaches for β-hemoglobinopathies [4].

In conclusion, Hbs1l is vital for ribosomal rescue and has a significant impact on retinal development and erythropoiesis. Studies using gene-knockout mouse models have revealed its role in congenital anomalies, developmental delay, retinal dystrophy, and its potential in modulating fetal hemoglobin levels, which is relevant to diseases like thalassemia and sickle cell disease [1,2,4,5].

References:

1. O'Connell, Amy E, Gerashchenko, Maxim V, O'Donohue, Marie-Francoise, Séraphin, Bertrand, Agrawal, Pankaj B. 2019. Mammalian Hbs1L deficiency causes congenital anomalies and developmental delay associated with Pelota depletion and 80S monosome accumulation. In PLoS genetics, 15, e1007917. doi:10.1371/journal.pgen.1007917. https://pubmed.ncbi.nlm.nih.gov/30707697/

2. Luo, Shiyu, Alwattar, Bilal, Li, Qifei, Chen, Jing, Agrawal, Pankaj B. 2024. HBS1L deficiency causes retinal dystrophy in a child and in a mouse model associated with defective development of photoreceptor cells. In Disease models & mechanisms, 17, . doi:10.1242/dmm.050557. https://pubmed.ncbi.nlm.nih.gov/38966981/

3. Stadhouders, Ralph, Aktuna, Suleyman, Thongjuea, Supat, Thein, Swee Lay, Soler, Eric. 2014. HBS1L-MYB intergenic variants modulate fetal hemoglobin via long-range MYB enhancers. In The Journal of clinical investigation, 124, 1699-710. doi:10.1172/JCI71520. https://pubmed.ncbi.nlm.nih.gov/24614105/

4. Chumchuen, Sukanya, Sripichai, Orapan, Jearawiriyapaisarn, Natee, Fucharoen, Suthat, Peerapittayamongkol, Chayanon. 2023. Induction of fetal hemoglobin: Lentiviral shRNA knockdown of HBS1L in β0-thalassemia/HbE erythroid cells. In PloS one, 18, e0281059. doi:10.1371/journal.pone.0281059. https://pubmed.ncbi.nlm.nih.gov/36888630/

5. Luo, Shiyu, Alwattar, Bilal, Li, Qifei, Chen, Jing, Agrawal, Pankaj B. 2023. Genetic deficiency of ribosomal rescue factor HBS1L causes retinal dystrophy associated with Pelota and EDF1 depletion. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.10.18.562924. https://pubmed.ncbi.nlm.nih.gov/37905068/