Humans and Old World monkeys have similar patterns of fetal globin expression

Abstract

The expression of ϵ‐ and γ‐globin mRNA and protein has been determined in three Old World monkey species (Macaca mulatta, Macaca nemestrina, and Cercopithecus aethiops). Using RT‐PCR with primers for ϵ‐ and γ‐globin, both mRNAs were detected in early fetal stages, whereas at 128 days (85% of full term), only γ was expressed. High‐performance liquid chromatography was used for separation and quantitation, and matrix‐assisted laser desorption/ionization mass spectrometry was used for identification of globin polypeptides. An α‐globin polymorphism was observed in all of the species examined. During fetal life, γ‐globin was the predominant expressed β‐type globin. The red blood cells of infants still contained substantial amounts of γ‐globin, which declined to negligible levels in 14 weeks as β‐globin expression reached adult values. The ratio of γ1‐ to γ2‐globins (equivalent to Gγ/Aγ in humans) was approximately 2.5, similar to the Gγ/Aγ ratio observed in humans. Thus, γ‐globin gene expression in these Old World monkeys species has three features in common with human expression: expression of both duplicated γ genes, the relative preponderance of γ1 over γ2 expression, and the delay of the switch from γ‐ to β‐globin until the perinatal period. Thus, the catarrhines seem to share a common pattern of developmental switching in the β‐globin gene cluster, which is distinct from the timing of expression in either prosimians or the New World monkeys. Our results indicate that an Old World monkey, such as Rhesus, could serve as a model organism (resembling humans) for experimentally investigating globin gene expression patterns during the embryonic, fetal, and postnatal stages. J. Exp. Zool. (Mol. Dev. Evol.) 288:318–326, 2000. © 2000 Wiley‐Liss, Inc.

Recent studies of iron deficiency during brain development in nonhuman primates

“…The iron content of rhesus monkey breast milk has been characterized [12], the ontogeny of hematopoiesis has been studied [13], and hematological reference ranges are available [14]. Evolutionary considerations also point up the value of nonhuman primate models in studying ID as a human biomedical model [13, 15–21].…”

Development of primitive and definitive hematopoiesis from nonhuman primate embryonic stem cells in vitro

“…In the erythrocytes of primates, the embryonic (ε and ζ), fetal (γ) and adult (β and α) globin genes are expressed sequentially during development, although small amounts of fetal and adult globin chains are detected even during primitive hematopoiesis (Johnson et al, 2000;Stamatoyannopoulos et al, 2001). Concomitant switches in the α cluster (replacement of the ζ globin gene by the α) and β cluster (replacement of the ε globin gene by the γ, and Although information about the development of primitive and definitive hematopoiesis has been elucidated in murine embryos and embryonic stem (ES) cells, there have been few in vitro studies of these processes in primates.…”

“…Old World monkeys, such as the cynomolgus monkey (Macaca fascicularis), are widely used for medical research (Hanazono et al, 2000) and have globin gene expression that is similar to that of humans (Johnson et al, 2000). Therefore, their ES cells might be used as a model for elucidating primate hematopoietic development.…”

Complex developmental patterns of histone modifications associated with the human β-globin switch in primary cells

“…Phylogenetic and expression analysis of humans and other mammals suggests that prior to recruitment for fetal expression, the γ-globins were active during embryonic erythropoiesis [43, 44, 45, 46]. The intermediate nature of γ gene expression is reflected in the lack of enrichment of positive marks, H3ac and H3K4me2, at the γ-globins in the absence of similar marks at either ε or β-globins.…”