From early development to maturity: a phenotypic analysis of the Townes sickle cell disease mice.

Abstract

Well-characterised mouse models of disease may provide valuable insights into pathophysiology. This study characterises the Townes mouse model of sickle cell disease (SCD) and establishes a time window in which the disease is present but does not progress significantly in terms of severity. We examined Townes mice with the HbAA, HbAS, and HbSS genotypes from young (4 weeks) to mature (5 months) stages of life to assess the disease state at different ages and any progression. We conducted blood tests, histological organ damage evaluations, and metabolic assessments to identify a suitable time frame for study based on welfare considerations. Townes HbSS mice displayed key SCD features such as anaemia, haemolysis, thromboinflammation and organ pathology. Notably, these manifestations remained relatively stable over the study period, indicating a stable phase suitable for conducting intervention studies. Mice with HbAS and HbAA genotypes served as comparative controls, showing minimal to no pathology throughout. These findings are valuable for future research on SCD and may ultimately lead to the development of more effective treatments for this debilitating disease.