Genetic mapping of a Ptch1-associated rhabdomyosarcoma susceptibility locus on mouse chromosome 2.
Mutations in the Patched (Ptch1) gene are responsible for various familial and sporadic cancers. Ptch1(neo67/+) mice, in which exons 6 and 7 are deleted, show genetic background-dependent susceptibility to the development of muscle tumors resembling human rhabdomyosarcoma (RMS); BALB/c (BALB) is a susceptible strain whereas C57BL/6 (B6) shows resistance. A genome-wide linkage analysis was carried out using Ptch1(neo67/+)mice produced from B6 x (BALB x B6) backcrosses to identify loci involved in the control of RMS susceptibility. Quantitative trait locus mapping with the censored tumor latency time as the quantitative parameter was used to detect a significant RMS susceptibility modifier locus, Parms1 (Patched-Associated RMS 1), on chromosome 2 between D2Mit37 and D2Mit102 (LRS = 10). A Kaplan-Meier survival curve revealed that mice with the B6/BALB genotype develop tumors more frequently and much faster as compared to mice homozygous for the B6 allele (P = 0.02). Additional loci not reaching linkage significance were also detected for medulloblastoma resistance.
Hahn
Heidi
H
Institute of Human Genetics, University of Göttingen, Heinrich-Düker-Weg 12, 37073 Göttingen, Federal Republic of Germany. hhahn@gwdg.de
Nitzki
Frauke
F
Schorban
Tatjana
T
Hemmerlein
Bernhard
B
Threadgill
David
D
Rosemann
Michael
M
D000818:Animals; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D003433:Crosses, Genetic; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011506:Proteins / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics; D011956:Receptors, Cell Surface; D012208:Rhabdomyosarcoma / Q000235:genetics*
D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011506:Proteins; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface