Arlm1^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Arlm1^C57BL/6J
• Name: astrocytoma resistance locus in males 1; C57BL/6J
• MGI ID: MGI:5766932
• QTL: Arlm1 Location: unknown Genetic Position: Chr12, Syntenic

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL

Notes

Males carrying homozygous B6 alleles were resistant to astrocytoma compared with males carrying heterozygous B6/129 alleles.

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

J:186764

NPcis mouse models carry alleles which modify the effects of mutant Nf1 and Trp53 genes in the development of astrocytoma. 129S4/SvJae-NPcis^pat mice show a significant delay in astrocytoma latency compared to C57BL/6J-Npcis^pat mice in both males and females.

The presence or absence of astrocytoma was mapped as a binary trait in a backcross using C57BL/6J-Npcis^pat x (C57BL/6J-Npcis^pat x 129S4/SvJae-NPcis^pat) mice. Males and females were considered separately and combined, but no increased linkage was observed in the commbined sexes, suggesting that genetic susceptibility to astrocytoma is linked to different loci in males and females.

A significant linkage peak named Arlm1, astrocytoma resistance locus 1, mapped to distal Chr 12 at 63.5 cM in males with a LOD=3.68, p=0.024. The 1.5 LOD support interval mapped between 53 and 63 cM.

This locus had no effect on female susceptipility to astrocytoma where as males carrying homozygous B6 alleles were resistant to astrocytoma compared with males carrying heterozygous B6/129 alleles.

In combining coding differences and expression level differences, at least 55 genes are likely to vary between B6 and 129 strains in the Arlm1 locus. Cdca7l is a strong candidate gene for Arlm1 along with 14 others of interest in this region: Itgb8, Dnah11, Ncapg2, SerpinA, Dicer1, Bcl11b, Evl, Pp2r5c, Xrcc3, Tdrd9, Cdca4, Jag2, Crip1 and Igh.

Arlm1 is syntenic to human Chr 7p15, 7p21, 7q36 and 14q32, regions that are altered in human glioblastoma.

References

• Original: J:186764 Amlin-Van Schaick JC, et al., Arlm1 is a male-specific modifier of astrocytoma resistance on mouse Chr 12. Neuro Oncol. 2012 Feb;14(2):160-74
• All: 1 reference(s)