title: Evidence that derivation of the adenocarcinoma LT85 predated establishment of the H-2km2 mutation in a C3Hf colony of mice.
abstract: The adenocarcinoma LT85 was chemically induced in a mouse from a C3Hf colony shown subsequently to be inbred for a gene conversion-like mutation at the H-2K locus, characterized by a clustered four nucleotide substitution in exon 3. The H-2K phenotype of LT85, however, more closely resembles that of C3H rather than the mutant strain now designated C3Hf H-2km2. We cloned and sequenced the H-2K gene from this tumor to determine whether (i) LT85 might carry a tumor-associated somatic reversion of the H-2Kkm2 germline mutation of (ii) the tumor was induced in a mouse that was genetically H-2k rather than H-2km2. Our analysis confirmed that the LT85 H-2K allele is identical throughout the entire coding region to C3H H-2Kk. To exclude the possibility of a somatic reversion by recombination, we used an oligonucleotide probe corresponding to the region altered in H-2k to show that the C3Hf genome lacks the necessary coding information to reverse the H-2Kkm2 mutation through a sequence exchange with another class I locus. Since it is unlikely that multiple independent point mutations would account for restoration of this stretch of H-2Kk sequences, the tumor was probably established in a mouse carrying a normal H-2Kk allele, possibly at a point prior to the establishment of the H-2Kkm2 mutation as a homozygous trait within the C3Hf colony.
authors.affiliation: Department of Genetics, University of California, Berkeley 94720.
authors.forename: J M
authors.initials: JM
authors.lastname: Vogel
authors.forename: M
authors.initials: M
authors.lastname: McMillan
authors.forename: W J
authors.initials: WJ
authors.lastname: Martin
authors.forename: R S
authors.initials: RS
authors.lastname: Goodenow
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002460:Cell Line; D003001:Cloning, Molecular; D006183:H-2 Antigens / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype
chemical_list: D006183:H-2 Antigens