Dataset Information

Alpha-fetoprotein related gene (ARG): a new member of the albumin gene family that is no longer functional in primates.

ABSTRACT: The serum albumin gene family is comprised of albumin, alpha-fetoprotein, alpha-albumin (afamin), and the more distantly related Vitamin D binding protein. These genes arose from a common ancestor through a series of duplication events, are expressed primarily in the liver and tightly linked in all species where this has been investigated. Here, we describe a fifth member of the albumin gene family that we have named Alpha-fetoprotein Related Gene (ARG) since it exhibits greatest similarity to this family member. ARG is activated in the liver perinatally, but is expressed at very low levels. The ARG gene is present and intact in the mouse, rat, dog and horse genomes. In contrast, the ARG gene in human, chimpanzee, rhesus monkey, and marmoset contains a number of mutations common to all four species, indicating that this gene has been an inactive pseudogene in primates for at least 40 million years. Low expression and aberrant splicing of the ARG gene in the mouse liver suggests that ARG may have less functional significance than other members of the serum albumin gene family even in species where it is still intact.

SUBMITTER: Naidu S

PROVIDER: S-EPMC2799041 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Alpha-fetoprotein related gene (ARG): a new member of the albumin gene family that is no longer functional in primates.

Naidu Sathyabama S Peterson Martha L ML Spear Brett T BT

Gene 20090903 1-2

The serum albumin gene family is comprised of albumin, alpha-fetoprotein, alpha-albumin (afamin), and the more distantly related Vitamin D binding protein. These genes arose from a common ancestor through a series of duplication events, are expressed primarily in the liver and tightly linked in all species where this has been investigated. Here, we describe a fifth member of the albumin gene family that we have named Alpha-fetoprotein Related Gene (ARG) since it exhibits greatest similarity to t ...[more]

PMID: 19733224

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Project description:Over the last two decades, enormous effort has been focused on developing virus-based gene delivery vectors to target the respiratory airway epithelium as a potential treatment for cystic fibrosis (CF) lung disease. However, amongst other problems, the efficiency of gene delivery to the differentiated airway epithelial cells of the lung has been too low for clinical benefit. Although not a target for CF therapy, the nasal epithelium exhibits cellular morphology and composition similar to that of the lower airways, thus representing an accessible and relevant tissue target for evaluating novel and improved gene delivery vectors. We previously reported that replication-competent human parainfluenza virus (PIV)-based vectors efficiently deliver the cystic fibrosis transmembrane conductance regulator gene to sufficient numbers of cultured CF airway epithelial cells to completely correct the bioelectric function of CF cells to normal levels, resulting in restoration of mucus transport. Here, using an in vitro model of rhesus airway epithelium, we demonstrate that PIV mediates efficient gene transfer in rhesus epithelium as in the human counterpart. Naive rhesus macaques were inoculated intranasally with a PIV vector expressing rhesus macaque ?-fetoprotein (rhAFP), and expression was monitored longitudinally. rhAFP was detected in nasal lavage fluid and in serum samples, indicating that PIV-mediated gene transfer was effective and that rhAFP was secreted into both mucosal and serosal compartments. Although expression was transient, lasting up to 10 days, it paralleled virus replication, suggesting that as PIV was cleared, rhAFP expression was lost. No adverse reactions or signs of discomfort were noted, and only mild, transient elevations of a small number of inflammatory cytokines were measured at the peak of virus replication. In summary, rhAFP proved suitable for monitoring in vivo gene delivery over time, and PIV vectors appear to be promising airway-specific gene transfer vehicles that warrant further development.

Dataset Information

Alpha-fetoprotein related gene (ARG): a new member of the albumin gene family that is no longer functional in primates.

Publications

Alpha-fetoprotein related gene (ARG): a new member of the albumin gene family that is no longer functional in primates.

Similar Datasets

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