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Full-Text Articles in Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Genomic Characterization Of Sickle Cell Mouse Models For Therapeutic Genome Editing Applications, Kaitly Jensen Woodard
Genomic Characterization Of Sickle Cell Mouse Models For Therapeutic Genome Editing Applications, Kaitly Jensen Woodard
Theses and Dissertations (ETD)
Sickle cell disease (SCD) is caused by a mutation of the β-globin gene (HBB), resulting in abnormal hemoglobin molecules that polymerize when deoxygenated, forming “sickle” shaped red blood cells (RBCs). Sickle RBCs lead to anemia, multi-organ damage and pain crises, beginning the first year of life. The onset of symptoms coincides with the developmental switch of β-like globin gene expression from fetal stage γ-globin to adult stage β-globin, resulting in a shift from fetal hemoglobin (HbF, α2γ2) to adult hemoglobin (HbA, α2β2). Some individuals harbor rare genetic variants in the extended β-globin gene cluster that cause constitutively elevated postnatal HbF, …
Stimulation Through Tlr4 Increases Fviii Inhibitor Formation In A Mouse Model Of Hemophilia A, Claire K. Holley
Stimulation Through Tlr4 Increases Fviii Inhibitor Formation In A Mouse Model Of Hemophilia A, Claire K. Holley
Dissertations & Theses (Open Access)
Hemophilia A is a clotting disorder caused by functional factor VIII (FVIII) deficiency. About 25% of patients treated with therapeutic recombinant FVIII develop antibodies (inhibitors) that render subsequent FVIII treatments ineffective. The immune mechanisms of inhibitor formation are not entirely understood, but circumstantial evidence indicates a role for increased inflammatory response, possibly via stimulation of Toll-like receptors (TLRs), at the time of FVIII immunization. I hypothesized that stimulation through TLR4 in conjunction with FVIII treatments would increase the formation of FVIII inhibitors. To test this hypothesis, FVIII K.O. mice were injected with recombinant human FVIII with or without concomitant doses …