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EVIDENCE THAT DERIVATION OF THE ADENOCARCINOMA LT85 PREDATED ESTABLISHMENT OF THE H‐2 km2 MUTATION IN A C3HF COLONY OF MICE
Author(s) -
Vogel J. M.,
McMillan M.,
Martin W. J.,
Goodenow R. S.
Publication year - 1989
Publication title -
international journal of immunogenetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.41
H-Index - 47
eISSN - 1744-313X
pISSN - 1744-3121
DOI - 10.1111/j.1744-313x.1989.tb00483.x
Subject(s) - biology , reversion , point mutation , genetics , locus (genetics) , germline , gene , allele , mutant , exon , microbiology and biotechnology , germline mutation , coding region , mutation , somatic cell , gene conversion , phenotype
SUMMARY 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‐2 km2 . 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‐2K km2 germline mutation or (ii) the tumor was induced in a mouse that was genetically H‐2 k rather than H‐2 km2 . Our analysis confirmed that the LT85 H‐2K allele is identical throughout the entire coding region to C3H H‐2K k . 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‐2K km2 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‐2K k sequences, the tumor was probably established in a mouse carrying a normal H‐2K k allele, possibly at a point prior to the establishment of the H‐2K km2 mutation as a homozygous trait within the C3Hf colony.