Mouse bone marrow and peripheral blood erythroid cell counts are regulated by different autosomal genetic loci

Abstract

1 SummaryErythropoiesis is under fine control and genetic loci that effect it are likely to be important in a range of conditions. To assess the relative contributions of different genetic loci to parameters of erythropoiesis we have measured RBC counts in the peripheral circulation and committed erythroid cells (RBC and small normoblasts) in the bone marrow in a cohort of (CBA/H x C57BL/6) F2 mice to map quantitative trait loci (QTL). Candidate genes were assessed using bioinformatics and DNA sequencing.Different autosomal loci affect bone marrow (chromosomes 5, 11, and 19) and peripheral blood (chromosome 4) erythroid cell counts but there may be a common chromosome X locus. Spleen weight QTL were found on chromosomes 3, 15 and 17. Surprisingly, erythropoietin (EPO) is the best candidate quantitative trait gene (QTG) in the chromosome 5 locus that affects bone marrow but not peripheral blood erythroid cell counts. Epo gene expression is known to be genetically regulated in mice, but our data suggests a tissue-specific role for epo in mouse erythropoiesis that is also genetically determined. The identity of the other QTG will be important both to further knowledge of the control of erythropoiesis and as potential modifier genes for haematological disorders.

Quantitative Trait Loci Analysis for Peripheral Blood Parameters in a (BALB/cW * C57BL/6J-Mpl hlb219/J) F2 Mice

“…The research began at the turn of the 21st century and has been continued by several groups of scientists. Until now, analyses of QTL influencing blood cells parameters have been conducted on groups of laboratory animals [1,7,12,14,16,21,26,27,39], but the same results have been obtained from examination of other mammals, such as swine [31,42] and baboons [3].…”

“…The highly significant QTL for RBC on chromosome 1, locus D1Mit218 (55.76cM, CI=19cM), is close to Rbcqtl1 [27], Pbrbc2 [14], or Rbcqtl2 [8]. Moreover, QTL for HCT, Hemq1 [16] situated in the vicinity (5cM) of QTL locus D1Mit218, and QTL for MCV, Mcvqtl1 [8], are in the determined confidence interval.…”

“…There is no evidence in the literature for a QTL for HCT on chromosome 4 (D4Mit14; 80.99cM), which was found in the present study. Two others QTLs for erythrocyte morphological parameters, Rbcq2 (70.47cM) [27] and Pbrbc1 (41.1cM) [14], are located on chromosome 4. As mentioned above, it could be the influence of the mutation in Mpl [6].…”

The stromal gene encoding the CD274 antigen as a genetic modifier controlling survival of mice with γ-radiation-induced T-cell lymphoblastic lymphomas

“…More recently, we evidenced that Anxa1, whose locus maps to the proximal part of the same Tlyr1 region, is able to confer significant resistance to g-radiation-induced thymic lymphomas (Santos et al, 2009). Several cancer predisposition loci that independently provide susceptibility or resistance to different types of cancer have been also mapped to the chromosome interval defined by Tlyr1 (Devereux et al, 1994;Matin et al, 1999;Jawad et al, 2007). These findings and the data reported in this study support the idea that cancer predisposition loci are organized into functional clusters containing multiple individual tumour resistance/susceptibility genes (Cormier et al, 2000;Wang et al, 2003a;Elahi et al, 2009).…”

QTL analyses of lineage-negative mouse bone marrow cells labeled with Sca-1 and c-Kit

“…For example, QTL that determine stem cell numbers (Henckaerts et al 2002(Henckaerts et al , 2004De Haan and Van Zant 1997, 2000Muller-Sieburg and Riblet 1996;Morrison et al 1997Morrison et al , 2002, the frequency of progenitor cells and the relative proportion of mature blood red, T and B cells (Chen and Harrison 2002;Morrison et al 2002;van Os et al 2006;Peters et al 2006;Valdar et al 2006;Jawad et al 2007a) have been identified. In a landmark study the gene underlying one of these QTL has recently been identified as latexin (Liang et al 2007).…”