Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  3
• Reference
  J:118331 Liang Y, et al., The quantitative trait gene latexin influences the size of the hematopoietic stem cell population in mice. Nat Genet. 2007 Feb;39(2):178-88
• ID
  MGI:3713343

Genes

Gene	Assay Type
Scpro6	visible phenotype
D3Mit5	PCR amplified length variant
Lxn	reported elsewhere

Notes

• Experiment
  Reciprocal congenic lines derived from DBA/2J and C57BL/6J were used to further examine Scpro6 (stem cell proliferation 6), a previously identified QTL at 24 cM on mouse Chromosome 3. Parental strain C57BL/6J exhibits increased stem cell proliferation and bone marrow repopulation capability compared to parental strain DBA/2J.
  
  The B6.D2-Scpro6 congenic line carries DBA/2J-derived DNA on chromosome 3 from 14 cM to 33 cM on a C57BL/6J genetic background. These animals display a 2-fold increase in whole-bone marrow cobblestone area forming cell (CAFC) numbers in vitro, and a 73% increase in long-term repopulating hematopoietic stem cells (HSCs) in vivo. The reciprocal congenic D2.B6-Scpro6 carries C57BL/6J-derived DNA on chromosome 3 from 19 cM - 60 cM on aDBA/2J genetic background. These animals display the reverse trend with a 40% decrease in day 35 CAFC numbers. The findings suggest that DBA/2J-derived alleles at Scpro6 increase HSC numbers whereas C57BL/6J-derived alleles decrease HSC numbers.
  
  The Scpro6 consensus interval was localized to a region spanning 36.5 Mb (19.2 cM) - 67.8 Mb (33 cM). The mostly highly correlated marker is D3Mit5 at 50.4 Mb (25 cM). Oligonucleotide array analysis was performed using bone marrow RNA derived from reciprocal congenic lines and progenitor strains C57BL/6J and DBA/2J to identify genes exhibiting differential expression. Lxn (31.6 cM) maps to the Scpro6 QTL interval and is upregulated in C57BL/6J and downregulated in DBA/2J. In addition an inverse correlation between Lxn expression and HSC numbers was observed in reciprocal congenic animals. B6.D2-Scpro6 congenic animals display decreased Lxn expression and increased HSC numbers while D2.B6-Scpro6 congenic animals display increased Lxn expression and decreased HSC numbers. Several SNPs were detected and confirmed in the Lxn potential upstream regulatory regions.
  
  In vitro overexpression of Lxn in bone marrow cells derived from DBA/2J and B6.D2-Scpro6 (both high HSC strains) reduced primitivestem cell frequencies byone-thirdcompared to the level of primitive stem cells observed in bone marrow cells transfected with a control-vector.
  
  Linkage analysis was performed using 30 BXD (B=C57BL/6J; D=DBA/2) recombinant inbred (RI) strains to identify QTLs regulating Lxn expression. A suggestive cis-acting QTL was detected at 56.9 Mb - 66.8 Mb on chromosome 3 near Lxn with C57BL/6J-derived alleles increasing Lxn expression. It is unclear whether this is a separate and distinct QTL from Scpro6.