Alterations in vascular reactivity in a transgenic mouse model of sickle cell trait

Skinner, Sarah; Liu, Kiao Ling; Josset-Lamaugarny, Audrey; Charrin, Emmanuelle; Martin, Cyril; Pialoux, Vincent; Fromy, Bérengère; Connes, Philippe; Sigaudo‐Roussel, Dominique

doi:10.1111/bjh.16577

Cited by 2 publications

(1 citation statement)

References 10 publications

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“…In this model, the murine adult α-globin and β-globin genes were replaced, respectively, with the human α-globin and the human sickle β S - genes. While the homozygous Townes mice are notoriously affected by SCD and have been well characterized, heterozygous “sickle-cell trait” mice, are not commonly used as a model of SCT [ 28 , 29 ]. It is well known that, in homozygous Townes mice, histopathological and hematological findings are the same that we could observe in the more severe human forms of SCD [ 30 ]; nevertheless, there is a lack of systematic and multi-organ data on the microanatomical alterations of SCT carrier mice.…”

Section: Introductionmentioning

confidence: 99%

Multi-Organ Morphological Findings in a Humanized Murine Model of Sickle Cell Trait

Trucas

Burattini

Porcu

et al. 2023

IJMS

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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.

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Section: Introductionmentioning

confidence: 99%