Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  19
• Reference
  J:81940 Ochiai Y, et al., Mapping of genetic modifiers of thymic lymphoma development in p53-knockout mice. Oncogene. 2003 Feb 20;22(7):1098-102
• ID
  MGI:3054219

Genes

Gene	Assay Type
Mp53d1	resistance/susceptibility
D19Mit5	PCR amplified length variant
Mp53d2	resistance/susceptibility
D19Mit90	PCR amplified length variant
Pten	reported elsewhere
Mp53d3	resistance/susceptibility
D19Mit123	PCR amplified length variant

Notes

• Experiment
  QTLs modifying thymic lymphoma development were mapped in 2 different backcross populations: one population consisted of (BALB/c-Trp53^tm1Brd x MSM)F1 x BALB/c animals and the other population consisted of (BALB/c-Trp53^tm1Brd x MSM)F1 x MSM animals. Tumors were induced by subjecting animals to gamma-irradiation. An initial screen for linkage was performed using 67 polymorphic markers at an average spacing of 24 cM. Mouse Chromosome 19 showed linkage to tumor development and additional markers and animalswere genotyped and phenotyped to map this locus.
  
  Linkage to thymic lymphoma development occurred at 3 loci on mouse Chromosome 19. The first peak mapped to 34 cM near D19Mit5 (P=0.0007) and is designated Mp53d1 (modifier of p53-deficiency 1). The secondpeak mapped to 41 cM near D19Mit90 (P=0.0007) and is designated Mp53d2. The third peak mapped to 51 cM near D19Mit123 (P=0.0003) and is designated Mp53d3. BALB/c-derived alleles appear to confer resistance to thymic lymphoma development at Mp53d3. Mp53d3 also shows linkage to skin tumor development with BALB/c-derived alleles conferring susceptibility to skin tumor development.
  
  Animals consomic for MSM-derived chromosome 19 on a BALB/c-Trp53^tm1Brd genetic background were created to confirm the presence ofMp53d1, Mp53d2, and Mp53d3. Consomic animals were subjected to gamma-irradiation and the effect of Mp53d2 at D19Mit90 was confirmed. BALB/c-derived alleles confer resistance to thymic lymphoma development at this locus. A possible candidate gene mappingnear Mp53d2 is Pten (24.5 cM). Authors speculate that Mp53d1 and Mp53d3 were not detected in the consomic study because of possible epistatic interactions.
  
  Allelic loss in thymic lymphoma samples was also examined (n=387). The region between D19Mit132 and D19Mit5 was found to have a 15.8% frequency of allele loss. This is near the vicinity of Mp53d2. However, allele loss did not favor either the BALB/c allele or the MSM allele. Authors speculate that if a tumor suppressor gene exists in this intervalitis likely to be distinct from Mp53d2.