Comparison of the polymorphic regions of the cytochrome P450 CYP2E1 gene of humans and patas and cynomolgus monkeys. (1/2)

Cytochrome P450 2E1 (CYP2E1) metabolizes low molecular weight toxicants. CYP2E1 gene polymorphisms have been linked to risk of various cancers and liver disease in humans. Since the patas monkey is a promising model for study of cancer-related alcohol/nitrosamine interactions, we examined CYP2E1 in this monkey for characteristics of two regions that are polymorphic in humans, an RsaI site in the 5' promoter region and a DraI site in intron 6. Another monkey species often used in biomedical research, the cynomolgus monkey, was also examined. Human DNA primers used to amplify a 413 bp segment around the RsaI site also amplified a segment of similar size (409 bp) from DNA of 25 patas monkeys, whereas a product of approximately 800 bp was amplified from DNA of eight cynomolgus monkeys. RsaI did not cut the amplified DNA product from either monkey species. Sequencing revealed that the patas RsaI site was identical to that in humans with the c2c2 CYP2E1 genotype, GTAT. The equivalent cynomolgus sequence, CTAC, has not been observed in humans. Thus, the patas monkey appears to be a useful model for CYP2E1 c2c2 humans, and this genotype, present in 2-25% of humans, may be more primitive than c1c1. For the DraI site, the human primers amplified DNA products similar in size to those from humans, from all patas and cynomolgus monkey DNA samples; none were cut by DraI. Thus, both monkey species appeared to be generally similar to humans of CYP2E1 CC DraI genotype, which is the rarer form of the gene.  (+info)

Adaptive and phylogenetic influences on musculoskeletal design in cercopithecine primates. (2/2)

Broad allometric studies of the musculoskeletal system have frequently sought to explain how locomotor variables have been influenced by body mass. To examine animals that vary widely in body mass, these studies have included taxa that differ in their locomotor adaptations and phylogenetic relatedness. Because these sources of diversity could obscure the effects of body mass, this study was designed to test the effects of adaptive differences in limb proportions and phylogeny, as well as body mass, on locomotor kinematics and extensor muscle mechanical advantage. More specifically, two hypotheses were tested in a sample of closely related animals: (i) that, among animals with similar body mass, those with longer limb segments should adopt more extended limb postures to moderate the joint and midshaft bending moments that they experience, and (ii) that body mass will have similar influences on joint posture and joint moments in closely related and diverse mammalian samples. Three-dimensional kinematic and synchronous force-platform data were collected for six individual cercopithecine monkeys ranging in mass from 4kg to 24kg and at a range of walking speeds. Comparisons among three monkeys with similar body mass but different limb segment lengths reveal a significant effect of limb proportion on posture. That is, animals with longer limbs frequently use more extended limb postures and can have correspondingly lower joint moments. The scaling of locomotor variables across the entire sample of closely related monkeys was generally similar to published results for a diverse sample of mammals, with larger monkeys having more extended limb postures, lower joint moments and greater effective mechanical advantage (EMA) for their limb extensor musculature. Ankle EMA, however, did not increase with body mass in the primate sample, suggesting that clade-specific adaptive differences (e.g. the use of arboreal supports by primates) may constrain the effects of body mass.  (+info)