Tb2r1^DBA/2J
QTL Variant Detail

Summary

• QTL variant: Tb2r1^DBA/2J
• Name: TGF-beta2 responsiveness 1; DBA/2J
• MGI ID: MGI:3029245
• QTL: Tb2r1 Location: Chr4:137674005-150676858 bp Genetic Position: Chr4, Syntenic

Variant origin

• Strain of Specimen: DBA/2J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers increased lin-Ska++kit+ (LSK) primitive progenitor cell numbers compared to C57BL/6J. This allele also confers decreased LSK cell responsiveness to TGF-beta2 stimulation, lower LSK cell frequency and decreased cycling of hemotopoietic stem and progenitor cells (HSPCs) compared to C57BL/6J (J:140749). (J:87437)

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:87437

30 BXD (C57BL/6J x DBA/2J) recombinant inbred strains (RI) were analyzed for QTLs linked to the regulation of lin-Ska++-kit+ (LSK) primitive progenitor cells by TGF-beta2. The effect of 0.1 ng/ml of TGF-beta2 on LSK cell proliferation was measured. A highly suggestive QTL associated with LSK cell number, Lskcn, mapped to approximately 73 cM on mouse Chromosome 4 between D4Mit158 (67 cM) and D4Mit33 (79 cM) with LRS=13.7. Interestingly this overlaps with a highly suggestive QTL associated with LSK cell number at 79 cM (LRS=15.9 at D4Mit33 and D4Mit343) previously identified by the same authors (see J:76791). DBA/2J-derived alleles confer increased LSK cell numbers at this locus.

J:92256

Linkage analysis was performed on aged BXD (B=C57BL/6J; D=DBA/2J) recombinant inbred (RI) animals to identify QTLs associated with hematopoiesis traits. The absolute number of Lin(-)Sca1(++)c-kit(+) cells (LSK phenotype) is 2-fold higher in C57BL/6J thanin DBA/2J. As the mice age the proliferative capacity of LSK cells decreases. This decrease in LSK responsiveness appears to be more pronounced in C57BL/6J than in DBA/2J.

Previously identified LSK QTLs on mouse Chromosomes 4 (Lskcn) and 7 (Lskcn2) wereconfirmed in this study. A locus on mouse Chromosome 2 (Hrec) was also confirmed in this study. The QTL interval of Lskcn2 spans 51 cM - 53 cM from D7Mit17 to D7Mit238. The DBA/2J-derived allele is associated with increased LSK number at 8 weeks of age for Lskcn2. A previously identified QTL named Scpro1 (stem cell proliferation 1) overlaps with Lskcn2 and could possibly be the same locus.

A suggestive lifespan QTL was detected at 69 cM - 72 cM on mouse Chromosome 2 between D2Mit396 and D2Mit304. This locus also shows linkage to stem cell proliferation at 18 months of age. The DBA/2J-derived allele is associated with increased lifespan and increased stem cell proliferation at 18 months. This locus maps near Hrec (75 cM) but is believed to be separate and distinct.

A suggestive locus at 38 cM - 48 cM on mouse Chromosome 4 was identified in linkage to LSK cell number at 18 months and lifespan. Peak linkage occurs between D4Mit80 and D4Mit303. The DBA/2J-derived allele is associated with increased lifespan whereas the C57BL/6J-derived allele is associated with increased LSK cell number.

Suggestive linkage to lifespan also mapped to 2 other intervals on mouse Chromosome 4. One locus is between 7.5 cM - 13 cM (D4Mit193 and D4Mit237) and the DBA/2J-derived allele is associated with increased lifespan. The other locus is between 70 cM - 82 cM (D4Mit312 and D4Mit344) and the C57BL/6J-derived allele is associated with increased lifespan.

A suggestive locus at 0.5 cM - 2.5 cM on mouse Chromosome 7 was identified in linkage to stem cell proliferation at 18 months of age. Peak linkage occurs between D7Mit78 and D7Mit190. This locus is also associated with lifespan. The DBA/2J-derived allele is associated with increased stem cell proliferation and increased lifespan at this locus.

A suggestive locus on mouse Chromosome 9 was identified in linkage to stem cell proliferation at 18 months of age. Peak linkage occurs between 23 cM - 27 cM. Markers associated with peak linkage are D9Mit227 and D9Mit4. The DBA/2J-derived allele is associated with increased stem cell proliferation.

A suggestive locus at 22 cM - 24 cM on mouse Chromosome 12 was identified in linkage to LSK cell number and %LSK cells at 18 months of age. The C57BL/6J-derived allele is associated with increased LSK cell number and %LSK cells at this locus.

A suggestive lifespan QTL was detected at 13 cM - 19 cM on mouse Chromosome 12 between D12Mit136 and D12Mit235. The DBA/2J-derived allele is associated with increased lifespan at this locus.

Suggestive linkage to LSK cell number at 8 weeks of age was detected on mouse Chromosomes 14 and 16 (at 20 cM). The chromosome 14 locus is very broad and no point of peak linkage was indicated. Peak linkage at the chromosome 16 locus occurs between D16Mit146 (16.9 cM) and D16Mit58 (23.1 cM).

A suggestive QTL associated with lifespan mapped to 63 cM - 73 cM on mouse Chromosome X between DXMit10 and DXMit223. DBA/2J-derived alleles are associated with increased lifespan at this locus.

References

• Original: J:87437 Langer JC, et al., Quantitative Trait Analysis Reveals Transforming Growth Factor-{beta}2 as a Positive Regulator of Early Hematopoietic Progenitor and Stem Cell Function. J Exp Med. 2004 Jan 5;199(1):5-14
• All: 4 reference(s)