title: Identification of quantitative trait loci regulating haematopoietic parameters in B6AKRF2 mice.
abstract: The haematopoietic system is a complex organised tissue with a hierarchical structure. Identification of organisational pathways within the haematopoietic system is relevant for a better understanding of haematopoiesis in health and disease. We have analysed numerous haematopoietic parameters in two panels of a total of 157 genetically distinct B6AKRF2 mice, derived from an intercross between AKR and C57Bl/6 mice, strains known to differ in various stem cell traits. The major objective of our study was to assess the extent to which various haematopoietic parameters, such as stem cell numbers, progenitor cell cycling, progenitor cell mobilisation and neutrophil numbers in blood and bone marrow are coregulated. The genotypes of these mice were used to search for genetic loci that regulate these parameters. We found significant quantitative trait loci (QTL) associated with the number of stem cells (CAFC-35) in the bone marrow and the number of neutrophils in the blood. However, most haematopoietic parameters appeared to be controlled by non-heritable (epigenetic) factors, or by multiple QTLs. Our study reveals striking differences in structure of the haematopoietic hierarchy between individual mice. Surprisingly, stem and progenitor cell pool size and proliferation rate, as well as peripheral blood cell counts are all independently regulated.
authors.affiliation: Department of Cell Biology, Section Stem Cell Biology, University Medical Centre Groningen, Groningen, The Netherlands. r.p.van.os@med.umcg.nl
authors.forename: Ronald
authors.initials: R
authors.lastname: van Os
authors.forename: Albertina
authors.initials: A
authors.lastname: Ausema
authors.forename: Estelle J K
authors.initials: EJ
authors.lastname: Noach
authors.forename: Kyrjon
authors.initials: K
authors.lastname: van Pelt
authors.forename: Bert J H
authors.initials: BJ
authors.lastname: Dontje
authors.forename: Edo
authors.initials: E
authors.lastname: Vellenga
authors.forename: Gerald
authors.initials: G
authors.lastname: de Haan
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D002874:Chromosome Mapping / Q000379:methods; D005838:Genotype; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000502:physiology; D007958:Leukocyte Count; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology; D016133:Polymerase Chain Reaction / Q000379:methods; D040641:Quantitative Trait Loci
chemical_list: D016179:Granulocyte Colony-Stimulating Factor