Met^Par4
QTL Variant Detail

Summary

• QTL variant: Met^Par4
• Name: met proto-oncogene; pulmonary adenoma resistance (susceptibility)
• MGI ID: MGI:2156626
• Synonyms: Par4^SWR/J
• QTL: Met Location: Chr6:17463799-17573979 bp, + strand Genetic Position: Chr6, 7.83 cM, cytoband A2

Variant origin

• Strain of Specimen: SWR/J

Variant description

• Allele Type: QTL
• Mutation: Nucleotide substitutions
• Mutation details: This allele confers lung tumor susceptibility compared to BALB/cJ. This allele differs from wild-type in the presence of Cys at amino acid residue 968 rather than Arg as in wild-type. The allele is present in the SWR/J and in SWR/Bm and is absent in all 77 other strains tested including BALB/c.
• Inheritance: Recessive

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:3876

Eighty seven progeny from a (A/J x C3H/He)F2 intercross were analyzed to map the following loci to mouse Chromosome 6: Met - Mtv23 - Cd8b1 - D6Mit10 - Raf1 - D6Mit13a - D6Mit14 - Pas1 - Kras - D6Int1. Only male progeny used. Authors map the QTL for a majorlung tumor susceptibilty gene (Pas1) between D6Mit10 and D6Int1 on mouse Chromosome 6 using linkage analysis of lung tumor susceptibilty in a (A/J x C3H/He)F2 intercross. Significant p values (0.0001) were obtained between Pas1 and D6Mit13, D6Mit14, Kras and D6Int1. Authors state Mtv23 had been previously reported to be near Cd8b1, however this study places it 1 cM distal to Met.

1.28.2016 Curator Note: Because Pas1 was mapped using AXB, BXA and (C57BL/6J x A/J)F2 mice, which differ from the mapping population used here, we condiser the current study a separate mapping experiment and have named this Pas14.

J:43176

To further define the genetics of predisposition and resistance to lung cancer in mice an intercross between the intermediately, susceptible BALB/cJ strain and the highly susceptible SWR/J strain was performed. Both parental strains carry the pulmonary adenoma susceptibility 1 (Pas1) locus, a major contributor to predisposition to lung cancer.

A whole genome scan was performed on 40 of the extreme-phenotype members of the (BALB/cJ x SWR/J) F2 mice. Phenotypes were genotyped using 231 markers covering all autosomes and Chromosome X.

Significant linkage was observed on Chromosome 6, peaking at D6Mit50 with a LOD score of 12.9 which explained ~25% of the total phenotypic variance with the BALB/cJ allele associated with decreased phenotype expression, reduced tumor multiplicity. The QTL was flanked by markers D6Mit123 and D6Mit138 (Fig.1); and labeled Par4.

J:37546

Linkage analysis was performed on 24 BXD (B=C57BL/6J; D=DBA/2J) recombinant inbred strains to identify loci associated with behavioral responses to methamphetamines. Several provisional QTLs were identified. The loci reported here are statistically significant to the level of P=0.001.

On mouse chromosome 1 a locus associated with change in body temperature mapped to 48.4 cM near D1Ncvs41 and a locus associated with climbing activity and body temperature change mapped to 74.5 cM near D1Ncvs12. These loci are designated Brmth1 (behavioral response to methamphetamines 1) and Brmth2, respectively.

On mouse Chromosome 5 a locus associated with chewing behavior mapped to 54 cM near D5Mit10. This locus is designated Brmth3.

On mouse Chromosome 6 loci associated with home cage activity mapped to 6 cM near Met and 31 cM near D6Nds3. These loci are designated Brmth4 and Brmth5, respectively.

On mouse Chromosome 7 a locus associated with home cage activity mapped to 66 cM near D7Mit12. This locus is designatedBrmth6.

On mouse Chromosome 9 a locus associated with home cage activity mapped to 16 cM near Fli1 and a locus associated with body temperature change mapped to 71 cM near D9Byu6. These loci are designated Brmth7 and Brmth8, respectively. The locus at Fli1 was also detected in separate studies by Tolliver et al (1994; J:21289) and Miner and Marley (1995; J:23071).

On mouse Chromosome 14 a locus associated with climbing activity mapped to 12.5 cM near D14Mit54. This locus is designated Brmth9.

On mouseChromosome 17 a locus associated with body temperature change mapped to 10.05 cM near Zfp40. This locus is designated Brmth10.

On mouse Chromosome 19 a locus associated with body temperature change mapped to 9 cM near Pomc1. This locus is designated Brmth11.

References

• Original: J:43176 Manenti G, et al., Genetic mapping of lung cancer modifier loci specifically affecting tumor initiation and progression. Cancer Res. 1997 Oct 1;57(19):4164-6
• All: 1 reference(s)