Mirb^C57BL/10J
QTL Variant Detail

Summary

• QTL variant: Mirb^C57BL/10J
• Name: modifier of macrophage iron burden; C57BL/10J
• MGI ID: MGI:3719203
• QTL: Mirb Location: unknown Genetic Position: Chr9, Syntenic

Variant origin

• Strain of Specimen: C57BL/10J

Variant description

• Allele Type: QTL
• Inheritance: Dominant

Notes

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

J:123506

Linkage analysis was performed on 192 (C57BL/10J x SWR/J)F2 animals and 96 (C57BL/10J x SWR/J)F1 x SWR/J backcross animals to identify genetic loci associated with tissue iron content. A panel of 159 polymorphic markers at a resolution of 7.9 cM was usedfor genome scan. Tissue iron content was evaluated at 8 weeks of age. Parental strain SWR/J displays increased liver and spleen iron content compared to parental strain C57BL/10J.

A highly significant locus for males, designated Mirb (modifier of macrophage iron burden), was identified on mouse Chromosome 9. Mirb is located between 76 Mb - 112 Mb and accounts for over one-third of the spleen iron variation. SWR/J-derived alleles at Mirb confer high spleen iron content in males with a recessive mode of inheritance.

B10.SWR-(D9Mit285-D9Mit151) congenic animals were constructed and subcongenic line analysis narrowed the Mirb region to a 322 kb interval between D9Mit278 (61 cM) and D9Mit184 (60 cM). There are 16 genes in this region, two of which (Mon1a, 4921517D21Rik) have sequence changes affecting conserved residues. On the basis of haplotype analysis, Mon1a and Mst1r (60 cM) were proposed as candidate genes.

C57BL strains carry a N374S amino substitution in Mon1a that is unique among inbred strains. Macrophages from C57BL/10J mice display greater ferroportin on the plasma membrane compared to B10.SWR-(D9Mit285-D9Mit151) congenic animals. In addition, Mon1a-specific interference RNA resulted in reduced expression of Mon1a and intracellular accumulationof ferroportin in macrophages of both C57BL/6J (C57BL/10J-like Mon1a allele) and A/J (SWR/J-like Mon1a allele).

B10.SWR-(D9Mit285-D9Mit151) congenic animals are also more susceptible to infection by Listeria monocytogenes, suggesting Mirb and/or Mon1a mayhave roles in both immune response and iron disorders.

References

• Original: J:123506 Wang F, et al., Genetic variation in Mon1a affects protein trafficking and modifies macrophage iron loading in mice. Nat Genet. 2007 Aug;39(8):1025-32
• All: 1 reference(s)