Nstr1^A/J
QTL Variant Detail

Summary

• QTL variant: Nstr1^A/J
• Name: nerve sheath tumor resistance QTL 1; A/J
• MGI ID: MGI:3663679
• QTL: Nstr1 Location: Chr19:5371140-5371338 bp Genetic Position: Chr19, cM position of peak correlated region/allele: 4.3 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: A/J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This paternally-inherited allele confers resistance to peripheral nerve sheath tumors compared to C57BL/6J. (J:105038)

Notes

Nstr1 modifies the effects of Nf1^tm1Tyj and Trp53^tm1Tyj.

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

J:105038

Modifiers of susceptibility to genetically modified peripheral nerve sheath tumors (GEM PNSTs) was investigated in 254 mice from a (C57BL/6J x A/J-Nf1^tm1TyjTrp53^tm1Tyj) x C57BL/6J backcross. Linkage analysis was performed with 105 polymorphic markersat an average spacing of 8 cM. When data was split into paternally- and maternally-inherited mutant alleles, linkage to tumor resistance was detected at 2 autosomal loci.

Significant linkage to paternally-inherited PNST resistance mapped to 0.5 cM on mouse Chromosome 19 to marker D19Mit59 (p=0.02). This locus is named Nstr1 (nerve sheath tumor resistance 1). Homozygosity for paternal C57BL/6J-derived alleles at Nstr1 confers tumor susceptibility, while the paternal A/J-derived allele confers resistance.Mtes1 (4 cM), a previously identified breast cancer metastasis locus, overlaps with Nstr1. This region is syntenic to human Chromosome 11q13, which has been associated with malignant peripheral nerve sheath tumors (MPNSTs) in humans.

Significant linkageto maternally-inherited PNST resistance mapped to 17.8 cM on mouse Chromosome 15 to marker D15Mit111 (p=0.05). This locus is named Nstr2 (nerve sheath tumor resistance 2). Maternal A/J-derived alleles at Nstr2 confer tumor resistance. This locus is syntenic to human Chromosome 8q, a region associated with MPNSTs in humans.

Previous studies identified an imprinted locus on mouse Chromosome 11 at 38 cM named Mastr (modifier of astrocytoma), which modulates the effects of Nf1^tm1Tyj and Trp53^tm1Tyj. This locus may be part of a network of epistatic interactions involving Nstr1 and Nstr2.

J:147432

Mouse Chromosome substitution strains (CSS) were informative in confirming the mapping of Nstr1 to mouse Chromosome 19. Nstr1 has a modifiying effect on peripheral nerve sheath tumors (PNSTs) which is evident in C57BL/6 J-NPcis mice. The Authors crossed C57BL/6J Chr 19^A/J/NaJ (B6-Chr19A) females to C57BL/6 J-NPcis B6-NPcis) males to generate B6-Chr19A X B6-NPcis (CSS19-NPcis^pat) progeny. The mating design is show figuratively in the text on page 216. The progeny showed a significant delay in tumor development confirming the contribution of a locus on chromosome 19.

References

• Original: J:105038 Reilly KM, et al., An imprinted locus epistatically influences Nstr1 and Nstr2 to control resistance to nerve sheath tumors in a neurofibromatosis type 1 mouse model. Cancer Res. 2006 Jan 1;66(1):62-8
• All: 1 reference(s)