Ptprj^Scc1-s
QTL Variant Detail

Summary

• QTL variant: Ptprj^Scc1-s
• Name: protein tyrosine phosphatase receptor type J; colon tumor susceptibility 1, susceptible
• MGI ID: MGI:2155183
• QTL: Ptprj Location: Chr2:90260098-90410939 bp, - strand Genetic Position: Chr2, 50.19 cM, cytoband E1-2

Variant origin

• Strain of Specimen: STS/A

Variant description

• Allele Type: QTL
• Mutation: Other
• Mutation details: Ptprj has been identified as the gene underlying the susceptibility to colon cancer phenotype. Mouse strains STS/A and BALB/cHea carry alleles of Scc1 conferring cancer susceptibility and resistance, respectively. Five amino acid substitutions have been identified between the strains, 2 conservative and 2 nonconservative substitutions in the extracellular domain and 1 conservative substitution in the intracellular domain. The STS/A haplotype also contains an insertion of 17 bp within intron 4. (J:77487)
• Inheritance: Not Specified

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

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

J:36996

QTL analysis of 192 (BALB/c x Ccs-19)F2 mice revealed two colon tumor susceptibility loci, Ptprj and Scc2, linked to D2Mit14a on mouse Chromosome 2. The best linkage is reported between Ptprj and D2MIt14a (P = 0.00004).

Authors suggest Tgfb2, Msh2, Apc and Grl1 as possible candidate genes for Scc2, Scc3, Scc4 and Scc5 respectively.

J:86054

Linkage analysis was performed on 314 (BALB/cHeA x Ccs-19/Dem)F2 intercross animals to identify QTLs associated with colon cancer susceptibility. Parental Ccs-19/Dem is a recombinant congenic strain derived from colon tumor susceptible STS/A and colon tumor resistant BALB/cHeA. F2 animals were treated with azoxymethan (AOM) to induce tumor formation and the number of tumors present was used to assess susceptibility. Previously identified colon cancer susceptibility loci Ptprj (formerly Scc1), Scc2, Scc3,Scc4, and Scc5 were detected and confirmed in this study. Interaction between Ssc4 and Ssc5 was confirmed. In addition, 5 novel susceptibility loci were identified as follows.

Scc11 mapped to 57 cM on mouse Chromosome 4 near D4Mit11. This locus appears have stronger tumor association in heterozygous female animals and BALB/cHeA-homozygous male animals. Scc11 also interacts with Scc3 on mouse Chromosome 1. Animals homozygous for STS/A-derived alleles at both Scc11 and Scc3 exhibit the greatest susceptibility to AOM-induced colon tumors.

Scc12 mapped to 63.5 cM on mouse Chromosome 7 near D7Mit67. This locus exhibits significant interaction with Scc5 on mouse Chromosome 18. Animals heterozygous at Scc12 and homozygous for STS/A-derived alleles at Ssc5 exhibit the greatest susceptibility to AOM-induced colon tumors. Scc12 also shows suggestive interaction with Scc3 on chromosome 1.

Scc13 mapped to 29 cM on mouse Chromosome 6 near D6Mit122 and shows interaction with Scc14 at 2 cM on mouse Chromosome 10 nearD10Mit75. Animals heterozygous at Scc13 and homozygous for STS/A-derived alleles at Scc14 exhibit the greatest susceptibility to AOM-induced colon tumors. Scc13 also shows suggestive interaction with Ptprj on mouse Chromosome 2, and Scc14 shows suggestiveinteraction with Scc4 on mouse Chromosome 17.

Scc15 mapped to 34 cM on mouse Chromosome 11 near D11Mit26. This locus shows interaction with Scc5 on mouse Chromosome 18. Animals homozygous for BALB/cHeA-derived alleles at Scc15 and heterozygous or homozygous for STS/A-derived alleles at Scc5 exhibit the greatest susceptibility to AOM-induced colon tumors.

References

• Original: J:36996 van Wezel T, et al., Gene interaction and single gene effects in colon tumour susceptibility in mice [see comments]. Nat Genet. 1996 Dec;14(4):468-70
• All: 5 reference(s)