Genetic variants in melanogenesis proteins TYRP1 and TYR are associated with the golden rhesus macaque phenotype.

Nonhuman primates (NHPs) are vital translational research models due to their high genetic, physiological, and anatomical homology with humans. The "golden" rhesus macaque (Macaca mulatta) phenotype is a naturally occurring, inherited trait with a visually distinct pigmentation pattern resulting in light blonde colored fur. Retinal imaging also reveals consistent hypopigmentation and occasional foveal hypoplasia.

Nonhuman primate genetic models for the study of rare diseases.

Pre-clinical research and development relies heavily upon translationally valid models of disease. A major difficulty in understanding the biology of, and developing treatments for, rare disease is the lack of animal models. It is important that these models not only recapitulate the presentation of the disease in humans, but also that they share functionally equivalent underlying genetic causes.

A novel non-human primate model of Pelizaeus-Merzbacher disease.

Pelizaeus-Merzbacher disease (PMD) is a severe hypomyelinating disorder of the central nervous system (CNS) linked to mutations in the proteolipid protein-1 (PLP1) gene. Although there are multiple animal models of PMD, few of them fully mimic the human disease. Here, we report three spontaneous cases of male neonatal rhesus macaques with the clinical symptoms of hypomyelinating disease, including intention tremors, progressively worsening motor dysfunction, and nystagmus.

Myelin-specific T cells in animals with Japanese macaque encephalomyelitis.

Objective: To determine whether animals with Japanese macaque encephalomyelitis (JME), a spontaneous demyelinating disease similar to multiple sclerosis (MS), harbor myelin-specific T cells in their central nervous system (CNS) and periphery.

Methods: Mononuclear cells (MNCs) from CNS lesions, cervical lymph nodes (LNs) and peripheral blood of Japanese macaques (JMs) with JME, and cervical LN and blood MNCs from healthy controls or animals with non-JME conditions were analyzed for the presence of myelin-specific T cells and changes in interleukin 17 (IL-17) and interferon gamma (IFNγ) expression.

Results: Demyelinating JME lesions contained CD4 T cells and CD8 T cells specific to myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), and/or proteolipid protein (PLP).

Spontaneous Gene Mutation in Rhesus Macaques (): A Novel Nonhuman Primate Model of Epidermolysis Bullosa Simplex.

Epidermolysis bullosa simplex (EBS) is an inherited skin disorder characterized by increased skin and mucous membrane fragility. Most cases are caused by mutations in keratin 5 () and keratin 14 (). Mutations of these genes result in cytoskeletal disruption of the basal keratinocytes.

Bardet-Biedl Syndrome in rhesus macaques: A nonhuman primate model of retinitis pigmentosa.

The development of therapies for retinal disorders is hampered by a lack of appropriate animal models. Higher nonhuman primates are the only animals with retinal structure similar to humans, including the presence of a macula and fovea. However, few nonhuman primate models of genetic retinal disease are known.

mGAP: the macaque genotype and phenotype resource, a framework for accessing and interpreting macaque variant data, and identifying new models of human disease.

Background: Non-human primates (NHPs), particularly macaques, serve as critical and highly relevant pre-clinical models of human disease. The similarity in human and macaque natural disease susceptibility, along with parallel genetic risk alleles, underscores the value of macaques in the development of effective treatment strategies. Nonetheless, there are limited genomic resources available to support the exploration and discovery of macaque models of inherited disease.

Embryonic atrazine exposure elicits proteomic, behavioral, and brain abnormalities with developmental time specific gene expression signatures.

Unlabelled: Atrazine (ATZ), the second most commonly used herbicide in the United States, is an endocrine disrupting chemical linked to cancer and a common drinking water contaminant. This study further investigates ATZ-related developmental toxicity by testing the following hypotheses in zebrafish: the effects of embryonic ATZ exposure are dependent on timing of exposure; embryonic ATZ exposure alters brain development and function; and embryonic ATZ exposure changes protein abundance in carcinogenesis-related pathways. After exposing embryos to 0, 0.

Whole genome sequencing predicts novel human disease models in rhesus macaques.

Rhesus macaques are an important pre-clinical model of human disease. To advance our understanding of genomic variation that may influence disease, we surveyed genome-wide variation in 21 rhesus macaques. We employed best-practice variant calling, validated with Mendelian inheritance.

Sex-specific characterization and evaluation of the Alzheimer's disease genetic risk factor sorl1 in zebrafish during aging and in the adult brain following a 100 ppb embryonic lead exposure.

Developmental lead (Pb) exposure is suggested in laboratory studies to be a trigger for neurodegenerative diseases such as Alzheimer's disease (AD). Sortilin-related receptor, L (DLR class) A repeats-containing (SORL1) is a recently identified AD genetic risk factor. SORL1 has limited characterization in vertebrate models in comparison to other AD genetic risk factors.

Directional and color preference in adult zebrafish: Implications in behavioral and learning assays in neurotoxicology studies.

The zebrafish (Danio rerio) is a useful vertebrate model organism for neurological studies. While a number of behavior and learning assays are recently reported in the literature for zebrafish, many of these assays are still being refined. The initial purpose of this study was to apply a published T-maze assay for adult zebrafish that measures how quickly an organism can discriminate between different color stimuli after receiving reinforcement to measure learning in a study investigating the later life impacts of developmental Pb exposure.

Embryonic ionizing radiation exposure results in expression alterations of genes associated with cardiovascular and neurological development, function, and disease and modified cardiovascular function in zebrafish.

The relationship between ionizing radiation (IR) and carcinogenesis is long established, but recently the association between IR and other diseases is starting to be recognized. Currently, there is limited information on the genetic mechanisms governing the role of IR in non-cancer related adverse health effects and in regards to an early developmental exposure. In this study, zebrafish embryos were exposed to a range of IR doses (0, 1, 2, 5, 10 Gy) at 26 h post fertilization (hpf).

A new model army: Emerging fish models to study the genomics of vertebrate Evo-Devo.

Many fields of biology--including vertebrate Evo-Devo research--are facing an explosion of genomic and transcriptomic sequence information and a multitude of fish species are now swimming in this "genomic tsunami." Here, we first give an overview of recent developments in sequencing fish genomes and transcriptomes that identify properties of fish genomes requiring particular attention and propose strategies to overcome common challenges in fish genomics. We suggest that the generation of chromosome-level genome assemblies--for which we introduce the term "chromonome"--should be a key component of genomic investigations in fish because they enable large-scale conserved synteny analyses that inform orthology detection, a process critical for connectivity of genomes.

Developmental reelin expression and time point-specific alterations from lead exposure in zebrafish.

Reelin (RELN) is a large glycoprotein that plays critical roles during and after neuronal development. In a previous study utilizing developing zebrafish, the RELN ortholog was in a subset of genes associated with neuronal function that was altered following exposure to 100ppb Pb at 72h post-fertilization (hpf). Although RELN is associated with neurodevelopment and neurological diseases, it represents a previously uncharacterized target for developmental Pb neurotoxicity.

Transcriptome alterations following developmental atrazine exposure in zebrafish are associated with disruption of neuroendocrine and reproductive system function, cell cycle, and carcinogenesis.

Atrazine, a herbicide commonly applied to agricultural areas and a common contaminant of potable water supplies, is implicated as an endocrine-disrupting chemical (EDC) and potential carcinogen. Studies show that EDCs can cause irreversible changes in tissue formation, decreased reproductive potential, obesity, and cancer. The U.

Extensive genetic diversity and substructuring among zebrafish strains revealed through copy number variant analysis.

Copy number variants (CNVs) represent a substantial source of genomic variation in vertebrates and have been associated with numerous human diseases. Despite this, the extent of CNVs in the zebrafish, an important model for human disease, remains unknown. Using 80 zebrafish genomes, representing three commonly used laboratory strains and one native population, we constructed a genome-wide, high-resolution CNV map for the zebrafish comprising 6,080 CNV elements and encompassing 14.

Decreased axonal density and altered expression profiles of axonal guidance genes underlying lead (Pb) neurodevelopmental toxicity at early embryonic stages in the zebrafish.

Previous studies have reported that environmental lead (Pb) exposure can result in neurological alterations in children leading to reduced IQ, attention deficit hyperactivity disorder, and diminished reading and learning abilities. However, the specific alterations in neurodevelopmental morphology and the underlying genetic mechanisms of these alterations have not yet been thoroughly defined. To investigate alterations in neurologic morphology and test the hypothesis that developmental Pb neurotoxicity is partially mediated through alterations in neuronal growth and transport function of axons, the changes of specific axon tracts in the embryonic zebrafish brain were observed with anti-acetylated α-tubulin staining at several developmental time points through 36hours post fertilization (hpf).

Global gene expression analysis reveals dynamic and developmental stage-dependent enrichment of lead-induced neurological gene alterations.

Background: The underlying genetic mechanisms specific to subtle neurological alterations associated with environmental lead (Pb) exposures have not been clearly elucidated.

Objectives: The goal of this study was to identify novel gene targets and the underlying genetic mechanisms associated with developmental Pb neurotoxicity.

Methods: We first exposed zebrafish embryos to a range of Pb concentrations throughout early development to establish relative toxicity.

Cancer cytogenetics in the zebrafish.

The zebrafish system has been established as a useful model for the study of carcinogenesis. The cytogenetic characterization of the genome is vital for furthering our understanding of the progression of the disease. Establishing a basic description of the zebrafish chromosomal karyotype and markers for each specific chromosome permitted the first cytogenetic characterization of the reference genome and the genome of cancer models.

Global gene expression analysis using a zebrafish oligonucleotide microarray platform.

Gene microarray technology permits quantitative measurement and gene expression profiling of transcript levels on a genome-wide basis. Gene microarray technology is used in numerous biological disciplines in a variety of applications including global gene expression analysis in relation to developmental stage, to a disease state, and in toxic responses. Herein, we include a demonstration of global gene expression analysis using a comprehensive zebrafish-specific oligonucleotide microarray platform.

RNA isolation from embryonic zebrafish and cDNA synthesis for gene expression analysis.

Many important and complex laboratory procedures require an input of high quality, intact RNA. A degraded sample or the presence of impurities can lead to disastrous results in downstream experimental applications. It is therefore, of utmost importance to use solid techniques with numerous safeguards and quality control checks to ensure a superior sample.