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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808161PMC
http://dx.doi.org/10.1182/blood-2008-03-143370DOI Listing

Publication Analysis

Top Keywords

congenic interval
20
b6sjl congenic
12
bone marrow
12
hematopoietic stem
8
stem cell
8
stromal cells
8
cells strains
8
congenic
7
cells
5
interval cd45/ly-5
4

Similar Publications

Article Synopsis
  • Dravet syndrome is a severe developmental and epileptic disorder marked by hard-to-control seizures, developmental delays, and a risk of sudden unexpected death in epilepsy (SUDEP).
  • Most cases are linked to genetic changes in the SCN1A gene, with different genetic and environmental factors affecting the severity of the disease.
  • Recent research identified specific genetic modifiers (Dsm2 and Dsm3) that impact the survival outcomes for Dravet syndrome, highlighting potential candidate genes that could be targeted for new treatments.
View Article and Find Full Text PDF

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 PDF

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 PDF

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 PDF

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.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!