The B6.SJL-Ptprc(d)Pep3(b)/BoyJ (B6.SJL) congenic mouse strain, a valuable and widely used tool in murine bone marrow transplantation studies, has long been considered equivalent to the parental C57B/L6 (B6) strain with the exception of a small congenic interval on chromosome 1 harboring an alternative CD45/Ly-5 alloantigen (Ly-5.1). In this study we compared functional properties of stem and stromal cells between the strains, and delineated the boundary of the B6.SJL congenic interval. We identified a 25% reduction in homing efficiency, 3.8-fold reduction in transplantable long-term hematopoietic stem cells (LT-HSCs), a 5-fold reduction in LT-HSCs capable of 24-hour homing, and a cell-intrinsic engraftment defect of 30% to 50% in B6.SJL-derived bone marrow cells relative to B6-derived cells. These functional differences were independent of stem cell number, cycling, or apoptosis. Genotypic analysis revealed a 42.1-mbp congenic interval in B6.SJL including 306 genes, and at least 124 genetic polymorphisms. Moreover, expression profiling revealed 288 genes differentially expressed between nonhematopoietic stromal cells of the 2 strains. These results indicate that polymorphisms between the B6 and SJL genotype within the B6.SJL congenic interval influence HSC engraftment and result in transcriptional variation within bone marrow stroma.
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http://dx.doi.org/10.1182/blood-2008-03-143370 | DOI Listing |
Mamm Genome
September 2024
Department of Pharmacology, Northwestern University Feinberg School of Medicine, 320 East Superior St., Searle 8-510, Chicago, IL, 60611, USA.
Mol Cell Probes
June 2024
Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address:
Allelic variation at the Ptprc gene, which encodes the pan-leukocyte marker CD45/Ly5, is commonly exploited to track hematopoietic reconstitution by flow cytometry in mixed bone marrow chimera transplant experiments. Historically, this was accomplished using bone marrow from C57BL/6 (Ptprc/CD45.2/Ly5.
View Article and Find Full Text PDFbioRxiv
April 2024
Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA 60611.
Dravet syndrome is a developmental and epileptic encephalopathy (DEE) characterized by intractable seizures, comorbidities related to developmental, cognitive, and motor delays, and a high mortality burden due to sudden unexpected death in epilepsy (SUDEP). Most Dravet syndrome cases are attributed to haploinsufficiency, with genetic modifiers and environmental factors influencing disease severity. Mouse models with heterozygous deletion of recapitulate key features of Dravet syndrome, including seizures and premature mortality; however, severity varies depending on genetic background.
View Article and Find Full Text PDFJ Immunol
March 2024
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville VA.
The MHC class I molecule H-2Dk conveys resistance to acute murine CMV infection in both C57L (H-2Dk transgenic) and MA/My mice. M.H2k/b mice are on an MA/My background aside from a C57L-derived region spanning the MHC (Cmv5s), which diminishes this resistance and causes significant spleen histopathology.
View Article and Find Full Text PDFFront Immunol
July 2023
Laboratory for Immunogenetics, Central Research TB Institute, Moscow, Russia.
Introduction: To dissect the role of the part of the complex comprised of the MHC-II genes in the control of tuberculosis (TB) infection, we previously established a panel of recombinant congenic mouse strains bearing different segments of the haplotype on the B6 ( ) genetic background. Fine genetic mapping, gene sequencing and assessment of TB phenotypes resulted in identification of the gene as a major factor of TB control.
Methods: We further narrowed the MHC-II interval by spotting a new recombination event, sequencing newly established DNA configuration and establishing a mouse strain B6.
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