Age and Genetic Background Modify Hybrid Male Sterility in House Mice

Widmayer, Samuel J.; Handel, Mary Ann; Aylor, David L.

doi:10.1534/genetics.120.303474

Cited by 20 publications

(21 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although this observation is in disagreement with a previous report that tested the fertility of the B6STUSF1 between 8-12 weeks of age 14 , a recent publication has highlighted age-dependent increases in fertility in hybrid strains of similar subspecies, starting at 15 weeks of age 15 , which we believe explains this discrepancy. Since it is the females of the Mus musculus musculus strain that need to be used as mothers for the production of the fully sterile STUSB6F1 hybrid, on account of the modifying locus on the Xchromosome, the production necessitates a breeding colony of STUS/Fore mice.…”

Section: Discussioncontrasting

confidence: 99%

Replacement of surgical vasectomy through the use of wild-type sterile hybrids

et al. 2021

View full text Add to dashboard Cite

For the production and rederivation of mouse strains, pseudopregnant female mice are used for embryo transfer and serve as surrogate mothers to support embryo development to term. Vasectomized males are commonly used to render pseudopregnancy in females, generated by surgical procedures associated with considerable pain and discomfort. Genetically modified mouse strains with a sterility phenotype provide a non-surgical replacement, and represent an important application of the 3Rs. However, the maintenance of such genetically modified mouse strains requires extensive breeding and genotyping procedures, which are regulated procedures under national legislation. As an alternative, we have explored the use of sterile male hybrids which result when two wild-type mouse subspecies, Mus musculus musculus and Mus musculus domesticus, interbreed. We find the male STUSB6F1 hybrid, resulting from the mating of female STUS/Fore with male C57BL/6J, ideally suited and demonstrate that its performance for the production of oviduct and uterine transfer recipients is indistinguishable when compared to surgically vasectomized mice. The use of these sterile hybrids avoids the necessity for surgical procedures or the breeding of sterile genetically modified lines and can be generated by the simple mating of two wild-type laboratory strains -a non-regulated procedure. Furthermore, in contrast with the breeding of genetically sterile mice, all male offspring are sterile and suitable for the generation of pseudopregnancy, allowing their efficient production with minimal breeding pairs. .

show abstract

Section: Discussioncontrasting

confidence: 99%

Replacement of surgical vasectomy through the use of wild-type sterile hybrids

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Metaphase arrest was previously found in several types of intersubspecific mouse hybrids (e.g., [61]); our results suggest that it may be affected by the loss of function of Prdm9. Age-dependent fertility has been detected in (PWK × B6)F1 mouse hybrids [6,62]. Their delayed meiosis was rescued by manipulating the copy number of Prdm9 [6].…”

Section: Discussionmentioning

confidence: 99%

Rat PRDM9 shapes recombination landscapes, duration of meiosis, gametogenesis, and age of fertility

et al. 2021

View full text Add to dashboard Cite

Background Vertebrate meiotic recombination events are concentrated in regions (hotspots) that display open chromatin marks, such as trimethylation of lysines 4 and 36 of histone 3 (H3K4me3 and H3K36me3). Mouse and human PRDM9 proteins catalyze H3K4me3 and H3K36me3 and determine hotspot positions, whereas other vertebrates lacking PRDM9 recombine in regions with chromatin already opened for another function, such as gene promoters. While these other vertebrate species lacking PRDM9 remain fertile, inactivation of the mouse Prdm9 gene, which shifts the hotspots to the functional regions (including promoters), typically causes gross fertility reduction; and the reasons for these species differences are not clear. Results We introduced Prdm9 deletions into the Rattus norvegicus genome and generated the first rat genome-wide maps of recombination-initiating double-strand break hotspots. Rat strains carrying the same wild-type Prdm9 allele shared 88% hotspots but strains with different Prdm9 alleles only 3%. After Prdm9 deletion, rat hotspots relocated to functional regions, about 40% to positions corresponding to Prdm9-independent mouse hotspots, including promoters. Despite the hotspot relocation and decreased fertility, Prdm9-deficient rats of the SHR/OlaIpcv strain produced healthy offspring. The percentage of normal pachytene spermatocytes in SHR-Prdm9 mutants was almost double than in the PWD male mouse oligospermic sterile mutants. We previously found a correlation between the crossover rate and sperm presence in mouse Prdm9 mutants. The crossover rate of SHR is more similar to sperm-carrying mutant mice, but it did not fully explain the fertility of the SHR mutants. Besides mild meiotic arrests at rat tubular stages IV (mid-pachytene) and XIV (metaphase), we also detected postmeiotic apoptosis of round spermatids. We found delayed meiosis and age-dependent fertility in both sexes of the SHR mutants. Conclusions We hypothesize that the relative increased fertility of rat versus mouse Prdm9 mutants could be ascribed to extended duration of meiotic prophase I. While rat PRDM9 shapes meiotic recombination landscapes, it is unnecessary for recombination. We suggest that PRDM9 has additional roles in spermatogenesis and speciation—spermatid development and reproductive age—that may help to explain male-specific hybrid sterility.

show abstract

“…There are many different autosomal regions that have been associated with hybrid sterility in house mice (e.g., Oka et al 2007;Good et al 2008a;White et al 2011;Turner and Harr 2014;Larson et al 2018b;Schwahn et al 2018;Morgan et al 2020;Widmayer et al 2020), but the primary genetic determinant of sterility in F1 hybrid males involves the rapid evolution of PRDM9 binding sites, the autosomal encoded protein that directs the location of recombination in mammals (Mihola et al 2009;Mukaj et al 2020). In F1 mouse hybrids, PRDM9 binds preferentially to ancestral binding sites, leading to the asymmetric formation of double strand breaks and autosomal asynapsis (Davies et al 2016;Gregorova et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Stage-specific disruption of X chromosome expression during spermatogenesis in sterile house mouse hybrids

Larson

Hunnicutt

Vanderpool

et al. 2021

Preprint

View full text Add to dashboard Cite

Hybrid sterility is a complex phenotype that can result from the breakdown of spermatogenesis at multiple developmental stages. Here, we disentangle two proposed hybrid male sterility mechanisms in the house mice, Mus musculus domesticus and M. m. musculus, by comparing patterns of gene expression in sterile F1 hybrids from a reciprocal cross. We found that hybrid males from both cross directions showed disrupted X chromosome expression during prophase of meiosis I consistent with a loss of Meiotic Sex Chromosome Inactivation (MSCI) and Prdm9-associated sterility, but that the degree of disruption was greater in mice with an M. m. musculus X chromosome consistent with previous studies. During postmeiotic development, gene expression on the X chromosome was only disrupted in one cross direction, suggesting that misexpression at this later stage was genotype-specific and not a simple downstream consequence of MSCI disruption which was observed in both reciprocal crosses. Instead, disrupted postmeiotic expression may depend on the magnitude of earlier disrupted MSCI, or the disruption of particular X-linked genes or gene networks. Alternatively, only hybrids with a potential deficit of Sly copies, a Y-linked ampliconic gene family, showed overexpression in postmeiotic cells, consistent with a previously proposed model of antagonistic coevolution between the X and Y-linked ampliconic genes contributing to disrupted expression late in spermatogenesis. The relative contributions of these two regulatory mechanisms and their impact on sterility phenotypes awaits further study. Our results further support the hypothesis that X-linked hybrid sterility in house mice has a variable genetic basis, and that genotype-specific disruption of gene regulation contributes to overexpression of the X chromosome at different stages of development. Overall, these findings underscore the critical role of epigenetic regulation of the X chromosome during spermatogenesis and suggest that these processes are prone to disruption in hybrids.

show abstract

Age and Genetic Background Modify Hybrid Male Sterility in House Mice

Cited by 20 publications

References 70 publications

Replacement of surgical vasectomy through the use of wild-type sterile hybrids

Replacement of surgical vasectomy through the use of wild-type sterile hybrids

Rat PRDM9 shapes recombination landscapes, duration of meiosis, gametogenesis, and age of fertility

Stage-specific disruption of X chromosome expression during spermatogenesis in sterile house mouse hybrids

Contact Info

Product

Resources

About