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Multi-Organ Morphological Findings in a Humanized Murine Model of Sickle Cell Trait
Marcello Trucas1, Sabrina Burattini2, Susanna Porcu3
1Department of Biomedical Sciences, Section of Cytomorphology, University of Cagliari, Cittadella Universitaria di Monserrato, 09042 Monserrato, Italy.
Insights
Sickle cell trait (SCT) carriers may experience organ damage, contrary to the belief that it is benign. This study found endothelial alterations in multiple organs of SCT mice, highlighting potential health risks.
Area of Science:
- Genetics
- Pathology
- Hematology
Background:
- Sickle cell disease (SCD) results from homozygous beta-globin gene mutation, causing organ damage and reduced lifespan.
- Sickle cell trait (SCT), a heterozygous mutation, is often considered benign, but recent evidence suggests potential pathological symptoms in carriers.
Purpose of the Study:
- To investigate morphological modifications and multi-organ damage in sickle cell trait carriers.
- To assess the suitability of the Townes mouse model for studying SCT-related histopathology.
Main Methods:
- Genotypic and hematological characterization of 13 heterozygous Townes mice.
- Histopathological analysis using conventional light microscopy and transmission electron microscopy (TEM).
Main Results:
- Ubiquitous endothelial alterations, including thickened vessel basal lamina, were observed in the lungs, liver, kidneys, and spleen of SCT mice.
- The lungs exhibited the most significant tissue architecture distortion, while the heart was least affected.
Conclusions:
- Heterozygous beta-globin gene mutation in SCT carriers can lead to widespread microscopic and ultrastructural tissue modifications.
- The Townes mouse model is a suitable translational tool for characterizing multi-organ involvement in sickle cell trait.
Abstract:
Sickle cell disease (SCD) is caused by the homozygous beta-globin gene mutation that can lead to ischemic multi-organ damage and consequently reduce life expectancy. On the other hand, sickle cell trait (SCT), the heterozygous beta-globin gene mutation, is still considered a benign condition. Although the mechanisms are not well understood, clinical evidence has recently shown that specific pathological symptoms can also be recognized in SCT carriers. So far, there are still scant data regarding the morphological modifications referable to possible multi-organ damage in the SCT condition. Therefore, after genotypic and hematological characterization, by conventional light microscopy and transmission electron microscopy (TEM), we investigated the presence of tissue alterations in 13 heterozygous Townes mice, one of the best-known animal models that, up to now, was used only for the study of the homozygous condition. We found that endothelial alterations, as among which the thickening of vessel basal lamina, are ubiquitous in the lung, liver, kidney, and spleen of SCT carrier mice. The lung shows the most significant alterations, with a distortion of the general tissue architecture, while the heart is the least affected. Collectively, our findings contribute novel data to the histopathological modifications at microscopic and ultrastructural levels, underlying the heterozygous beta-globin gene mutation, and indicate the translational suitability of the Townes model to characterize the features of multiple organ involvement in the SCT carriers.
