The quantitative trait gene latexin influences the size of the hematopoietic stem cell population in mice

Abstract

We mapped quantitative trait loci that accounted for the variation in hematopoietic stem cell (HSC) numbers between young adult C57BL/6 (B6) and DBA/2 (D2) mice. In reciprocal chromosome 3 congenic mice, introgressed D2 alleles increased HSC numbers owing to enhanced proliferation and self-renewal and reduced apoptosis, whereas B6 alleles had the opposite effects. Using oligonucleotide arrays, real-time PCR and protein blots, we identified latexin (Lxn), a gene whose differential transcription and expression was associated with the allelic differences. Expression was inversely correlated with the number of HSCs; therefore, ectopic expression of Lxn using a retroviral vector decreased stem cell population size. We identified clusters of SNPs upstream of the Lxn transcriptional start site, at least two of which are associated with potential binding sites for transcription factors regulating stem cells. Thus, promoter polymorphisms between the B6 and D2 alleles may affect Lxn gene expression and consequently influence the population size of hematopoietic stem cells.

Genetic Background Affects Properties of Satellite Cells and mdx Phenotypes

“…Recombinant inbred mice, named BXD strains, are available. Using BXD, Liang et al 37 identified latexin as affecting the size of the hematopoietic stem cell population in mice. A similar approach might lead to the discovery of key genes that affect the properties of satellite cells.…”

Latexin exhibits tumor suppressor potential in hepatocellular carcinoma

“…However, its sequence is unrelated to any other reported CPIs, but shows significant homology with the putative tumor suppressor, tazarotene-induced gene 1 (TIG1), suggesting a familial relationship (13,15). Liang et al revealed that latexin functions in the negative control of hematopoietic stem cell (HSC) populations in mice by decreasing cell replication and increasing apoptosis (16). Latexin-deficient HSCs have been shown to possess an enhanced colony-forming ability (17).…”

The genetic basis of variation in susceptibility to infection with Histoplasma capsulatum in the mouse

“…[6][7][8] Inbred mice differ in their susceptibilities to fungal pathogens, including H. capsulatum. [9][10][11][12] We explored mouse susceptibility differences using intranasal inoculation, reasoning that a route of infection that mimics the natural course of disease might reveal information about disease progression, and observed a large difference in fungal burden between the inbred A/J and C57BL/6J strains.…”