Dataset Information

Functional polymorphisms in rhesus macaque FCGRT and ?2-m.

ABSTRACT: Rhesus macaque is an important animal model for studies testing interventions like antibody therapeutics; as such knowledge of inter-individual variations in function of genes affecting antibody recycling is important for optimal experimental design. Neonatal Fc receptor (FcRn), a heterodimer composed of FCGRT and ?2-m chains, plays critical role in extending catabolic half-life of IgG. We studied genomic polymorphisms in rhesus macaque FcRn and asked if they are functional by assessing correlations with serum IgG or ?2-m levels. We tested 75 animals and report the presence of a VNTR polymorphism in promoter of FcRn as well as a single nucleotide polymorphism in the signal peptide of ?2-m. A VNTR minor allele was associated with lower levels of serum IgG. This polymorphism may account for inter-animal variation in antibody levels and has relevance for effective design of rhesus macaque studies investigating vaccine-induced antibody responses and passive immunizations.

SUBMITTER: Shubin Z

PROVIDER: S-EPMC5823023 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Functional polymorphisms in rhesus macaque FCGRT and β2-m.

Shubin Zhanna Z Tagaya Yutaka Y Poonia Bhawna B

Immunogenetics 20170807 3

Rhesus macaque is an important animal model for studies testing interventions like antibody therapeutics; as such knowledge of inter-individual variations in function of genes affecting antibody recycling is important for optimal experimental design. Neonatal Fc receptor (FcRn), a heterodimer composed of FCGRT and β2-m chains, plays critical role in extending catabolic half-life of IgG. We studied genomic polymorphisms in rhesus macaque FcRn and asked if they are functional by assessing correlat ...[more]

PMID: 28785825

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Project description:PurposeAnimal models are powerful tools to broaden our understanding of disease mechanisms and to develop future treatment strategies. Here we present detailed structural and functional findings of a rhesus macaque suffering from a naturally occurring bilateral macular dystrophy (BMD), partial optic atrophy and corresponding reduction of central V1 signals in visual fMRI experiments when compared to data in a healthy macaque (CTRL) of similar age.MethodsRetinal imaging included infrared and autofluorescence recordings, fluorescein and indocyanine green angiography and spectral domain optical coherence tomography (OCT) on the Spectralis HRA + OCT platform. Electroretinography included multifocal and Ganzfeld-ERG recordings. Animals were killed and eyes analyzed by immunohistochemistry.ResultsAngiography showed reduced macular vascularization with significantly larger foveal avascular zones (FAZ) in the affected animal (FAZBMD = 8.85 mm(2) vs. FAZCTRL = 0.32 mm(2)). OCT showed bilateral thinning of the macula within the FAZ (total retinal thickness, TRTBMD = 174 ± 9 µm) and partial optic nerve atrophy when compared to control (TRTCTRL = 303 ± 45 µm). Segmentation analysis revealed that inner retinal layers were primarily affected (inner retinal thickness, IRTBMD = 33 ± 9 µm vs. IRTCTRL = 143 ± 45 µm), while the outer retina essentially maintained its thickness (ORTBMD = 141 ± 7 µm vs. ORTCTRL = 160 ± 11 µm). Altered macular morphology corresponded to a preferential reduction of central signals in the multifocal electroretinography and to a specific attenuation of cone-derived responses in the Ganzfeld electroretinography, while rod function remained normal.ConclusionWe provided detailed characterization of a primate macular disorder. This study aims to stimulate awareness and further investigation in primates with macular disorders eventually leading to the identification of a primate animal model and facilitating the preclinical development of therapeutic strategies.

Dataset Information

Functional polymorphisms in rhesus macaque FCGRT and ?2-m.

Publications

Functional polymorphisms in rhesus macaque FCGRT and β2-m.

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