International Mammalian Genome Society

The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

E34 Unexpectedly High Recombination Frequency in a Cross Involving an Interspecies Congenic Strain on Chr X During Genetic Analysis of Male Hybrid Subfertility

Rosemary W. Elliott, Darla R. Miller1, R. Scott Pearsall2, Colleen Hohman, Diane Poslinski, Debra A. Tabaczynski, Verne M. Chapman. Roswell Park Cancer Inst., Buffalo NY 14263 USA; 1Tennessee Mouse Genome Consortium, Oak Ridge, TN, USA; 2Vanderbilt University Medical Center, Department of Cell Biology, Nashville, TN 37232, USA

A hybrid congenic strain, C57BL/6J.Spret-Hprta, also called AT24, carrying 20 map units of Chr X from M. spretus on a background of C57BL/6J has the novel phenotype of subfertility or semisterility, associated with small testis weight (0.11 g for AT24 vs 0.21 gm for C57BL/6J). About half of the tubules in the testes of these congenic mice are empty of all cells, including spermatogonia and Sertoli cells, while the other tubules appear to be normal. The finding of interspecific hybrid semifertility is of great interest because it suggests that the speciation process may involve difficulties in protein-protein interactions in the development of male germ cells. The identification of the gene function of Ihtw1 (interspecific hybrid testis weight 1) and the genes with which it interacts will be important in unraveling the molecular events in sperm development, and identifying developmental sites and stages that are vulnerable in interspecies hybrids.

To fine map Ihtw1, a series of eleven subcongenic strains were generated from recombinants within the congenic region after crossing AT24 with C56BL/6J. The recombination frequency within the congenic region was only 17% of the frequency expected, suggesting that most recombination on Chr X occurred in DNA from C57BL/6J, outside the congenic region. Subsequent recombination during the development of the subcongenic strains generated four secondary subcongenic strains. Genetic analysis of the 15 subcongenic strains using microsatellite primers and PCR has been used to map the ends of the subcongenic regions. Phenotyping the subcongenic strains by measuring testis weights and comparison with the subcongenic ends has defined a critical region of 0.9 map units for Ihtw1, an interval which is suitable for physical mapping. Several genes are found in this interval, but there is no obvious candidate gene. However, Ihtw1 is a candidate for the human Borjeson-Forssman-Lehman syndrome (BFLS), which maps in the orthologous region of human Chr X and is characterized by low testis weight and mental retardation.

Construction of a single subcongenic strain carrying M. spretus DNA for only the critical region was initiated by crossing two subcongenic strains with overlapping inserts from M. spretus. Among the first 47 progeny from this cross there were 12 crossovers in the nominal 1 map unit overlap interval, giving a recombination frequency of 25.5%, much higher than expected. This finding of a hot spot of recombination in mouse may begin to make the study of mammalian meiosis more amenable to cytological and molecular analysis.

(Supported by PHS grant GM 33160 to RWE).


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