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Publication : Genetic and molecular analysis of chlorambucil-induced germ-line mutations in the mouse.

First Author  Rinchik EM Year  1990
Journal  Proc Natl Acad Sci U S A Volume  87
Issue  4 Pages  1416-20
PubMed ID  2304907 Mgi Jnum  J:10322
Mgi Id  MGI:58775 Doi  10.1073/pnas.87.4.1416
Citation  Rinchik EM, et al. (1990) Genetic and molecular analysis of chlorambucil-induced germ-line mutations in the mouse. Proc Natl Acad Sci U S A 87(4):1416-20
abstractText  Eighteen variants recovered from specific locus mutation rate experiments involving the mutagen chlorambucil were subjected to several genetic and molecular analyses. Most mutations were found to be homozygous lethal. Because lethality is often presumptive evidence for multilocus-deletion events, 10 mutations were analyzed by Southern blot analysis with probes at, or closely linked to, several of the specific locus test markers, namely, albino (c), brown (b), and dilute (d). All eight mutations (two c; three b; two d; and one dilute-short ear [Df(d se)]) that arose in post-spermatogonial germ cells were deleted for DNA sequences. No evidence for deletion of two d-se region probes was obtained for the remaining two d mutations that arose in stem-cell spermatogonia. Six of the primary mutants also produced low litter sizes (semisterility). Karyotypic analysis has, to date, confirmed the presence of reciprocal translocations in four of the six. The high frequency of deletions and translocations among the mutations induced in post-spermatogonial stages by chlorambucil, combined with its overall high efficiency in inducing mutations in these stages, should make chlorambucil mutagenesis useful for generating experimentally valuable germ-line deletions throughout the mouse genome.
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