DOI: 10.5061/dryad.m0cfxppdr
title: Data from : From early development to maturity: A phenotypic analysis of the Townes sickle cell disease mice

description: Well-characterized mouse models of disease may provide valuable insights
 into pathophysiology. This study characterizes 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 relative 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.
description: # Data from : From early development to maturity: A phenotypic analysis of
 the Townes sickle cell disease mice
 [https://doi.org/10.5061/dryad.m0cfxppdr](https://doi.org/10.5061/dryad.m0cfxppdr) ## Description of the data and file structure Data was collected from in vivo studies on the Townes mouse model of Sickle cell disease and AI-based algorithms to classify liver H&E tissue sections. Raw data obtained from mouse in vivo experiments and AI-trained liver tissue classifier ### Files and variables ## File: Dataset.csv **Description:** Raw in vivo data. .csv: Utilized for organizing and presenting data summaries by genotype, month and sex. Each .csv file is part of a different type of parameters analysed: * Haematological parameters: All blood related parameters * HE: hematoxilin & eosin liver staining, tissue classifier outputs * IHC: Immunohistochemistry of  P-selectin and von Willebrand Factor (vWF) in liver and lung * Thrombogram: of each individual sample over time * Thrombin generation: main readouts of each thrombogram * Cytokines: refer to plasma cytokines ## Haematological parameters This dataset contains comprehensive haematological and organ measurements collected from Townes mice with various genotypes over multiple months. The dataset includes a range of blood parameters, organ weights, and ratios, as well as some biochemical markers. The data is organized into the following columns: * **Genotype**: The genotype of the mice (HbSS, HbAS, HbAA). * **Month**: The age of the mice (by month) when the data was collected. * **Sex**: The sex of the subjects (M for male, F for female). * **WBC (10^9/L)**: White Blood Cell count. * **RBC (10^12/L)**: Red Blood Cell count. * **HGB (mmol/L)**: Hemoglobin concentration. * **HCT (%)**: Hematocrit percentage. * **MCV (fL)**: Mean Corpuscular Volume. * **MCH (amol)**: Mean Corpuscular Hemoglobin. * **MCHC (mmol/L)**: Mean Corpuscular Hemoglobin Concentration. * **PLT (10^9/L)**: Platelet count. * **NEUT# (10^9/L)**: Neutrophil count. * **LYMPH# (10^9/L)**: Lymphocyte count. * **MONO# (10^9/L)**: Monocyte count. * **RET# (10^12/L)**: Reticulocyte count. * **RET (%)**: Reticulocyte percentage. * **LFR (%), HFR (%)**: Low and High Fluorescence Ratio percentages. * **Organ Weights and Ratios**: Weights and ratios for spleen, liver, brain, heart, kidney, lung. * **Last BW**: Last body weight recorded. * **Ratios**: Organ weight ratios relative to body weight. * **Biochemical Markers**: * **CREA2 (mmol/L)**: Creatinine levels. * **ALP2L (U/L)**: Alkaline Phosphatase levels. * **ALTL (U/L)**: Alanine Aminotransferase levels. * **ASTL (U/L)**: Aspartate Aminotransferase levels. * **FERR4 (ug/L)**: Ferritin levels. * **BILT (umol/L)**: Total Bilirubin levels. * **BILD2**: Direct Bilirubin levels. #### Notes * All measurements are given in their respective units as indicated in the column headers. * Data is collected over multiple months, allowing for longitudinal analysis. ### HE This dataset contains information on the HE liver tissue classifier outputs from mice with various genotypes over multiple months. The data is organized into the following columns: * **Month**: The age of the mice (by month) when the data was collected. * **Genotype**: The genotype of the subjects (e.g., HbSS, HbAS, HbAA). * **Sex**: The sex of the subjects (M for male, F for female). * **% Clot of RBC**: The percentage of total tissue classified as red blood cell clots. * **% Necrotic tissue**: The percentage of total tissue classified as necrotic tissue. * **% Diseased liver tissue**: The percentage of total tissue classified as diseased liver tissue. ### ICH This dataset contains information on the percentage of P-selectin and von Willebrand Factor (vWF) in liver and lung tissues from mice with various genotypes over multiple months. The data is organized into the following columns: * **Genotype**: The genotype of the mice (e.g., HbSS, HbAS, HbAA). * **Month**: The age of the mice (by month) when the data was collected. * **Tissue**: The type of tissue sampled (e.g., Liver, Lungs). * **Stain**: P-selectin IHC measurement. * **% of P-selectin**: The percentage of P-selectin in the tissue. * **Stain2**: vWF ICH measurement. * **% of vWF**: The percentage of von Willebrand Factor in the tissue. ### Thrombin generation This dataset contains detailed thrombin generation parameters and thrombograms for mice with different genotypes. The data includes measurements of Peak Thrombin, Endogenous Thrombin Potential (ETP), and time-series thrombin generation data for various subjects. The data is organized into the following columns: * **Genotype**: The genotype of the subjects (e.g., HbSS, HbAS, HbAA). * **Peak thrombin (nM)**: The peak concentration of thrombin generated, measured in nM. * **ETP**: Endogenous Thrombin Potential, an integral of the thrombin generation curve. ### Thrombograms Time-series data of thrombin generation for each sample. * **Time**: Time points at which thrombin generation was measured. * **HbSS, HbSS2, HbSS3, ..., HbAA10**: Thrombin generation values for individual subjects at each time point. ### Cytokines This dataset contains immunological data collected from Townes mice with the HbSS/HbAS/HbAA genotype over multiple months. The dataset comprises various cytokine and chemokine levels measured in pg/ml. The data is organized into the following columns: * **Genotype**: The genotype of the mice: HbSS/HbAS/HbAA * **Month**: The age of the mice (by month) when the data was collected. * **TNF-a**: Tumor Necrosis Factor alpha levels. * **IL-5**: Interleukin 5 levels. * **IL-6**: Interleukin 6 levels. * **IL-10**: Interleukin 10 levels. * **KC/GRO**: Keratinocyte-derived chemokine/Growth-regulated oncogene levels. * **IL-1b**: Interleukin 1 beta levels. * **IL-2 pg/ml**: Interleukin 2 levels measured in pg/ml. * **IFN-y**: Interferon gamma levels. * **LLOQ**: Lower Limit of Quantification, which has been adjusted by taking LLOQ/2. #### Notes * The LLOQ values have been adjusted by dividing them by 2, as indicated in the dataset. * All cytokine and chemokine levels are measured in pg/ml. * Empty cells/null represent lack of data ## Code/software ## Halo AI Image analysis software v3.5 (Indica Labs) liver tissue classifiers **Tissue detection v2.1 classifier - Random forest algorithm:** First classifier applied for tissue and background identification. **Infarct identification_ver4 classifier - DenseNet V2:** Second classifier applied on the classified tissue from the tissue detection classifier. Classifies the tissue in 5 categories: background, normal healthy liver tissue, red blood cells clot, infarcted area (necrotic tissue) and diseased liver tissue (which included areas with inflammation, extramedullary proliferation and bile duct proliferation).