Mouse t-Complex Recombination: Challenges and Promises

Naturally occurring variant forms of the t-complex, known as complete t-haplotypes, are found in 25 % of wild mouse populations, Mus musculus. The t-haplotypes contain at least four non-overlapping inversions, In(17)1 through In(17)4. These inversions contain several functionally related mutant genes. These mutations affect or control such diverse properties as embryonic development, meiotic transmission ratio, tail length, spermatogenesis, and recombination suppression. The focus of this proposal is the fourth inversion of the t-complex (In[17]4) which contains many important loci. The four paracentric inversions prevent recombination. Although, recombination events will be prevented by the presence of the chromosomal inversions, previous studies in our lab suggested that recombination may be taking place in the middle of In(17)4. Our central hypothesis is that recombination frequency within the t-complex could change based on the wild type homolog used in the cross and is not always suppressed due to the paracentric chromosomal inversions as has been previously thought. To test this hypothesis we performed PCR analysis, along with PCR-based restriction site (PBR), and genetics crosses to perform an analysis of a 4.1-million base pair (Mbp) segment in the middle of In(17)4. Our results showed that inversions suppressed the frequency of recombination in the RF and CAST mouse strain crosses when the recombination was within the inverted region. However, the frequency of recombination was much higher in +/+ mice higher than +/t. This frequency was surprisingly even higher when the male was heterozygous especially that mice are heterochiasmatic. We conclude that recombination frequency is suppressed within inverted regions and increased in non-inverted regions, which was in turn influenced by the gender of the heterozygous parent