Tmrb1^DBA/2J
QTL Variant Detail

Summary

• QTL variant: Tmrb1^DBA/2J
• Name: trace metal regulation in brain 1; DBA/2J
• MGI ID: MGI:3794753
• QTL: Tmrb1 Location: unknown Genetic Position: Chr14, Syntenic

Variant origin

• Strain of Specimen: DBA/2J

Variant description

• Allele Type: QTL

Notes

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

J:135429

Linkage analysis was performed on 805 animals from 28 BXD/TyJ recombinant inbred (RI) strains to identify QTL associated with hippocampal concentrations of Fe (iron), Cu (copper) and Zn (zinc). Approximately 13 animals per sex from each RI line were phenotyped at 120-days old. Progenitor strain C57BL/6J displays higher hippocampal zinc concentration and lower hippocampal iron and copper concentrations compared to DBA/2J.

Significant linkage to hippocampal copper concentration in female animals mapped to 38.7 Mb (13.5 cM) on mouse Chromosome 14 near SNP marker rs6197032 (LOD=4.69). This locus is named Tmrb1 (trace metal regulation in brain 1). Suggestive linkage to hippocampal copper concentration in males (LOD=3.39) and iron concentration in females (LOD=2.59) also map to Tmrb1. The Tmrb1 QTL interval spans 38.7 Mb (13.5 cM) to 47.2 Mb (15 cM). C57BL/6J-derived alleles at Tmrb1 confer increased hippocampal copper concentration. Samd4 at 46 Mb (14 cM) is a potential candidate gene for Tmrb1. Expression of Samd4 exhibits positive correlated with hippocampal iron, copper and zinc concentrations in female mice, and positive correlated with hippocampal copper concentration in male mice. Appd1 (21 cM) is an amyloid precursor protein (APP)-associated lethality QTL located near Tmrb1.

Suggestive linkage to hippocampal copper and zinc concentration in male animals mapped to 40.2 Mb (17 cM) on mouse Chromosome 9 near rs6240566 (LOD=3.39 and 2.73, respectively). This locus is named Tmrb2 (trace metal regulationin brain 2). The QTL interval spans 30.9 Mb (12 cM) to 50.9 Mb (29 cM). C57BL/6J-derived alleles at Tmrb2 confer increased hippocampal copper and zinc concentrations. Potential candidate genes located in this interval include Tbcel at 42.2 Mb (formerly Lrrc35) and D60033011Rik (*note- this gene symbol is not found in MGI) at 43 Mb. The gene expression pattern of Tbcel and D60033011Rik exhibit negative correlation to hippocampal iron,copper and zinc levels in male mice. Appd2 (11 cM) is a previously identified QTL located near Tmrb2. Authors hypothesize variations in brain copper homeostasis may indirectly influence APP-associated lethality and neurotoxicity. Bace1 (45.6 Mb) is a gene located in the overlapping QTL intervals of Tmrb2 and Appd2, and therefore being considered as a candidate.

References

• Original: J:135429 Jones LC, et al., Genetic analysis reveals polygenic influences on iron, copper, and zinc in mouse hippocampus with neurobiological implications. Hippocampus. 2008;18(4):398-410
• All: 1 reference(s)