Molecular Characterization of Skeletal Muscle Dysfunction in Sigma 1 Receptor (Sigmar1) Knockout Mice.

Sigma 1 receptor (Sigmar1) is a widely expressed, multitasking molecular chaperone protein that plays functional roles in several cellular processes. Mutations in the Sigmar1 gene are associated with several distal neuropathies with strong manifestation in skeletal muscle dysfunction with phenotypes like muscle wasting and atrophy. However, the physiological function of Sigmar1 in skeletal muscle remains unknown. Herein, the physiological role of Sigmar1 in skeletal muscle structure and function in gastrocnemius, quadriceps, soleus, extensor digitorum longus, and tibialis anterior muscles was determined. Quantification of myofiber cross-sectional area showed altered myofiber size distribution and changes in myofiber type in the skeletal muscle of the Sigmar1-/- mice. Interestingly, ultrastructural analysis by transmission electron microscopy showed the presence of abnormal mitochondria, and immunostaining showed derangements in dystrophin localization in skeletal muscles from Sigmar1-/- mice. In addition, myopathy in Sigmar1-/- mice was associated with an increased number of central nuclei, increased collagen deposition, and fibrosis. Functional studies also showed reduced endurance and exercise capacity in the Sigmar1-/- mice without any changes in voluntary locomotion, markers for muscle denervation, and muscle atrophy. Overall, this study shows, for the first time, a potential physiological function of Sigmar1 in maintaining healthy skeletal muscle structure and function.

Variable rates of hybridization among contact zones between a pair of topminnow species, Fundulus notatus and F. olivaceus.

Pairs of species that exhibit broadly overlapping distributions, and multiple geographically isolated contact zones, provide opportunities to investigate the mechanisms of reproductive isolation. Such naturally replicated systems have demonstrated that hybridization rates can vary substantially among populations, raising important questions about the genetic basis of reproductive isolation. The topminnows, Fundulus notatus and F. olivaceus, are reciprocally monophyletic, and co-occur in drainages throughout much of the central and southern United States. Hybridization rates vary substantially among populations in isolated drainage systems. We employed genome-wide sampling to investigate geographic variation in hybridization, and to assess the possible importance of chromosome fusions to reproductive isolation among nine separate contact zones. The species differ by chromosomal rearrangements resulting from Robertsonian (Rb) fusions, so we hypothesized that Rb fusion chromosomes would serve as reproductive barriers, exhibiting steeper genomic clines than the rest of the genome. We observed variation in hybridization dynamics among drainages that ranged from nearly random mating to complete absence of hybridization. Contrary to predictions, our use of genomic cline analyses on mapped species-diagnostic SNP markers did not indicate consistent patterns of variable introgression across linkage groups, or an association between Rb fusions and genomic clines that would be indicative of reproductive isolation. We did observe a relationship between hybridization rates and population phylogeography, with the lowest rates of hybridization tending to be found in populations inferred to have had the longest histories of drainage sympatry. Our results, combined with previous studies of contact zones between the species, support population history as an important factor in explaining variation in hybridization rates.