Identification of quantitative trait loci that modify the severity of hereditary spherocytosis in wan, a new mouse model of band-3 deficiency
| Autor: | Renhua Li, Gary A. Churchill, Luanne L. Peters, Babette Gwynn, Samuel E. Lux, Amy J. Lambert, Rebecca A. Swearingen, Sabra G. Andersen |
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| Rok vydání: | 2004 |
| Předmět: |
Erythrocyte Indices
Candidate gene Quantitative Trait Loci Immunology Mean corpuscular hemoglobin Spherocytosis Hereditary Hematocrit Quantitative trait locus Biochemistry Hereditary spherocytosis Mice Anion Exchange Protein 1 Erythrocyte medicine Animals Humans Band 3 Mean corpuscular volume Crosses Genetic Genetics Mice Inbred C3H Base Sequence biology medicine.diagnostic_test Membrane Proteins Spectrin Blood Proteins DNA Cell Biology Hematology medicine.disease Mice Mutant Strains Cytoskeletal Proteins Disease Models Animal Red blood cell Phenotype medicine.anatomical_structure Codon Terminator biology.protein Lod Score |
| Zdroj: | Blood. 103:3233-3240 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Defects in red blood cell (RBC) membrane skeleton components cause hereditary spherocytosis (HS). Clinically, HS varies significantly even among individuals with identical gene defects, illustrating the profound effects of genetic background on disease severity. We exploited a new spontaneous mouse model, wan, which arose on the inbred C3H/HeJ strain, to identify quantitative trait loci (QTL) that modify the HS phenotype. Homozygous wan mice have severe HS due to a complete deficiency of erythroid band 3. A QTL analysis of RBC count, hemoglobin, hematocrit, mean corpuscular volume (MCV), and mean corpuscular hemoglobin content (MCHC) was performed in wan/wan mice from an F2 intercross between C3H/HeJ+/wan and CAST/Ei+/+ F1 hybrids. Hematologic and survival data from C3H, CAST/Ei F2 wan homozygotes support the hypothesis that genetic modifiers significantly influence the band-3 null HS phenotype. Significant QTL were identified for the MCV trait only, suggesting that RBC membrane characteristics are a target for modifier gene action. The most significant quantitative trait locus, Hsm1 (hereditary spherocytosis modifier 1), localizes to mouse Chromosome 12 and is dominant. The peak LOD score was obtained with a marker for Spnb1 encoding erythroid β-spectrin, an obvious candidate gene. (Blood. 2004;103: 3233-3240) |
| Databáze: | OpenAIRE |
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