Mtes1^AKR/J
QTL Variant Detail

Summary

• QTL variant: Mtes1^AKR/J
• Name: Metastasis efficiency suppressor gene 1; AKR/J
• MGI ID: MGI:2388802
• QTL: Mtes1 Location: unknown Genetic Position: Chr19, Syntenic

Variant origin

• Strain of Specimen: AKR/J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers suppression of mammary tumor metastasis compared to DBA/2J. (J:73358)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Candidate Genes

J:103849

The authors showed a representation of approximately 110kb of gemomic mouse Chromosome 19. The markers were ordered as Centromere - Rela - Sipa1 - Pcnxl3 - Map3k11 - Kcnk7 - Telomere. Evidence is also provided using the two strains of mice with high metastatic efficiency (AKR/J and FVB/NJ) and the two strains with low metastatic efficiency (DBA/2J and NZB/B1NJ) that mouse Sipa1 may be a candidate for QTL Mtes1.

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

J:73358

18 AKXD (AK = AKR/J; D = DBA/2J) recombinant inbred (RI) strains and the following backcrosses were used to map loci associated with suppression of mammary tumor metastasis: (I/LnJ x FVB/N-TgN(MMTVPyVT)634Mul)F1 x FVB/NJ, (DBA/2J x FVB/N-TgN(MMTVPyVT)634Mul)F1 x FVB/NJ, and (NZB/BINJ x FVB/N-TgN(MMTVPyVT)634Mul)F1 x FVB/NJ. Significant linkage to mammary tumor metastasis mapped to proximal mouse Chromosome 19 near Slc3a2 (LOD = 3.6) at approximately 4 cM in the AKXD RI strains, and was named Mtes1 (Metastasis efficiency suppressor gene 1). Mtes1 reached suggestive linkage in the (NZB/BINJ x FVB/N-TgN(MMTVPyVT)634Mul)F1 x FVB/NJ backcross (LOD = 2.3) but not in the other 2 backcrosses. AKR/J-derived alleles appear to confer metastasic suppression at Mtes1. A possible candidate gene for Mtes1 is Brms1.

J:97671

Previously identified loci showing suggestive linkage to modification of mammary tumors induced by the mouse mammary tumor virus polyomavirus middle T antigen (MMTV-PyVT) were studied further using chromosome substitution strains (CSSs). Separate lines were created using I/LnJ or NZB/BlNJ as the donor strain for mouse Chromosomes 7, 9, 17, and 19 and FVB/NJ as the recipient strain. The following consomic lines were investigated: FVB/NJ-Chr 7^I/LnJ, FVB/NJ-Chr 9^I/LnJ, FVB/NJ-Chr 9^NZB/BlNJ, FVB/NJ-Chr17^NZB/BlNJ, and FVB/NJ-Chr 19^NZB/BlNJ.

Each CSS strain was crossed to the transgenic FVB/N-Tg(MMTV-PyVT)634Mul/J to observe modification of tumor latency. Only the chromosome 7 congenic, FVB/NJ-Chr 7^I/LnJ, when crossed to FVB/N-Tg(MMTV-PyVT)634Mul/J showed acceleration of mammary tumor progression, or decreased tumor latency. This finding confirms the previously identified suggestive mammary tumor modifier on mouse Chromosome 7 near D7Mit246 (15 cM). This locus is named Mmtp1 (modifier of mammary tumor progression 1). The FVB/NJ-Chr 7^I/LnJ CCS also exhibits reduced tumor mass, confirming the presence of a previously identified QTL named Mmtg3 (modifier of mammary tumor growth 3) at 3 cM. Mmtg3 is believed to be separate and distinct from Mmtp1.

The chromosome 9 consomic line FVB/NJ-Chr 9^I/LnJ exhibits a 20% decrease in mammary tumor burden compared to control strain FVB/N-Tg(MMTV-PyVT)634Mul/J. These animals also exhibit decreased number and size of metastatic pulmonary tumors when crossed toFVB/NJ-Tg(MMTV-PyVT)634Mul/J. This result supports the existence of a previously mapped suggestive locus near D9Mit207 (33 cM) and is designated Mmtp3 (modifier of mammary tumor progression 3). The FVB/NJ-Chr 9^NZB/BlNJ consomic line shows stronger association with the number and size of metastatic pulmonary tumors compared to the FVB/NJ-Chr 9^I/LnJ consomic line.

The chromosome 17 consomic line FVB/NJ-Chr 17^NZB/BlNJ exhibits a 44% decrease in mammary tumor burden compared to control strain FVB/N-Tg(MMTV-PyVT)634Mul/J. This locus may be the same as a previously identified tumor growth modifier near D17Mit81 (16.4 cM) and is designated Mmtp2 (modifier of mammary tumor progression 2). Mmtp2 is also associated with decreased number and size of metastatic pulmonary tumors.

The chromosome 19 consomic line FVB/NJ-Chr 19^NZB/BlNJ exhibits a26%decrease in mammary tumor burden compared to control strain FVB/N-Tg(MMTV-PyVT)634Mul/J. The number and size of pulmonary metastases is also reduced in consomic animals and confirms the presence of a previously identified QTL named Mtes1 (metastasis efficiency suppressor gene 1) at 4 cM.

References

• Original: J:73358 Hunter KW, et al., Predisposition to efficient mammary tumor metastatic progression is linked to the breast cancer metastasis suppressor gene Brms1. Cancer Res. 2001 Dec 15;61(24):8866-72
• All: 1 reference(s)