Hypercholesterolemia induced by spontaneous oligogenic mutations in rhesus macaques (Macaca mulatta)

[Background] A rhesus macaque with the fourth highest plasma cholesterol (CH) levels of 501 breeding macaques was identified 22 years ago. Seven offspring with gene mutations causing hypercholesterolemia were obtained. [Methods] Activity of low-density lipoprotein receptor (LDLR), plasma CH levels and mRNA expression levels of LDLR were measured after administration of 0.1% (0.27 mg/kcal) or 0.3% CH. [Results] Activity of p. (Cys82Tyr) of LDLR was 71% and 42% in the heterozygotes and a homozygote, respectively. The mRNA expression level of LDLR in the p. (Val241Ile) of membrane-bound transcription factor protease, site 2 (MBTPS2, S2P protein) was 0.83 times lower than normal levels. LDLR mRNA levels were increased for up to 4 weeks by administration of 0.3% CH before suddenly decreasing to 80% of the baseline levels after 6 weeks. [Conclusion] Oligogenic mutations of p. (Cys82Tyr) in LDLR and p. (Val241Ile) in MBTPS2 (S2P) caused hypercholesterolemia exceeding cardiovascular risk levels under a 0.1% CH diet

One-Step PCR To Distinguish B Virus from Related Primate Alphaherpesviruses

By adding betaine to the PCR mixture, we previously established a PCR method to amplify a DNA segment of the glycoprotein G gene of B virus (BV) derived from a rhesus macaque. We have found that DNA of other BV strains derived from cynomolgus, pigtail, and lion-tailed macaques can also serve as the template in our PCR assay. Under the same conditions no product was obtained with DNA of simian agent 8 of green monkeys and Herpesvirus papio 2 of baboons, or the human herpes simplex viruses types 1 and 2. Thus, this PCR method is useful to discriminate BV from other closely related primate alphaherpesviruses

Human-specific SNP in obesity genes, adrenergic receptor beta2 (ADRB2), Beta3 (ADRB3), and PPAR γ2 (PPARG), during primate evolution.

UnlabelledAdrenergic-receptor beta2 (ADRB2) and beta3 (ADRB3) are obesity genes that play a key role in the regulation of energy balance by increasing lipolysis and thermogenesis. The Glu27 allele in ADRB2 and the Arg64 allele in ADRB3 are associated with abdominal obesity and early onset of non-insulin-dependent diabetes mellitus (NIDDM) in many ethnic groups. Peroxisome proliferator-activated receptor γ (PPARG) is required for adipocyte differentiation. Pro12Ala mutation decreases PPARG activity and resistance to NIDDM. In humans, energy-expense alleles, Gln27 in ADRB2 and Trp64 in ADRB3, are at higher frequencies than Glu27 and Arg64, respectively, but Ala12 in PPARG is at lower frequency than Pro12. Adaptation of humans for lipolysis, thermogenesis, and reduction of fat accumulation could be considered by examining which alleles in these genes are dominant in non-human primates (NHP). All NHP (P. troglodytes, G. gorilla, P. pygmaeus, H. agilis and macaques) had energy-thrifty alleles, Gly16 and Glu27 in ADRB2, and Arg64 in ADRB3, but did not have energy-expense alleles, Arg16, Gln27 and Trp64 alleles. In PPARG gene, all NHP had large adipocyte accumulating type, the Pro12 allele.ConclusionsThese results indicate that a tendency to produce much more heat through the energy-expense alleles developed only in humans, who left tropical rainforests for savanna and developed new features in their heat-regulation systems, such as reduction of body hair and increased evaporation of water, and might have helped the protection of entrails from cold at night, especially in glacial periods

Two Tetranucleotide Repeats within the Xq21.3/Yp11.2 Human Specific Region of Homology and Their Conservation in Primate Evolution

We locate two tetranucleotide repeat sequences (AT3 and T2C2) between the markers sY44 and sY46 within the Xq21.3/Yp block of homology that has been created since the separation of the chimpanzee and human lineages, and trace their origin in primate evolution. The T2C2 repeat is present only in hominoid primates. The sequence AT3 is present in Old World monkeys but not in New World monkeys, and has been lost in some gibbon species. In the bonobo, the AT3 repeat is the site of a new Alu insertion. These findings and their relationship to the conservation of other markers in this region cast light on the structure of a genomic region that has been subject to change in the course of primate evolution and may include one or more sites of instability

Molecular Events in Immune Responses to Sublingual Influenza Vaccine with Hemagglutinin Antigen and Poly(I:C) Adjuvant in Nonhuman Primates, Cynomolgus Macaques

Sublingual vaccines offer the benefits of inducing mucosal immunity to protect against respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and influenza, while also enabling needle-free self-administration. In a previous study, a sublingual SARS-CoV-2 vaccination was created by combining a recombinafigureCoV-2 spike protein receptor-binding domain antigen with a double strand RNA Poly(I:C) adjuvant. This vaccine was tested on nonhuman primates, Cynomolgus macaques. This study examined the immune and inflammatory responses elicited by the sublingual influenza vaccine containing hemagglutinin (HA) antigen and Poly(I:C) adjuvants, and assessed the safety of this vaccine in nonhuman primates. The Poly(I:C)-adjuvanted sublingual vaccine induced both mucosal and systemic immunities. Specifically, the sublingual vaccine produced HA-specific secretory IgA antibodies in saliva and nasal washings, and HA-specific IgA and IgG were detected in the blood. This vaccine appeared to be safe, as judged from the results of blood tests and plasma C-reactive protein levels. Notably, sublingual vaccination neither increased the production of inflammation-associated cytokines—IFN-alpha, IFN-gamma, and IL-17—in the blood, nor upregulated the gene expression of proinflammatory cytokines—IL12A, IL12B, IFNA1, IFNB1, CD69, and granzyme B—in white blood cells. Moreover, DNA microarray analyses revealed that sublingual vaccination evoked both enhancing and suppressing expression changes in genes associated with immune-related responses in cynomolgus monkeys. Therefore, the sublingual vaccine with the Poly(I:C) adjuvant is safe, and creates a balanced state of enhancing and suppressing the immune-related response

All hominoids had <i>Gly16</i> allele in <i>ADRB2</i>.

<p>A) Restriction map of <i>ADRB2</i> for the 16^th amino acid digested with <i>BsrD</i>I (GCAATGNN). This restriction map was predicted from the nucleotide sequences of hominoids (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043461#pone-0043461-g001" target="_blank">Fig. 1</a>). B) RFLP patterns of PCR products of <i>ADRB2</i> for the 16^th amino acid digested with <i>BsrD</i>I in hominoids. Lane 1: PCR product of a human; not digested (200 bp). Lane 2: Fragments of human <i>Arg16/Gly16</i> (130,108 and 56 bp (22 and 14 bp fragments were undetectable)). Lane 3 to lane 6: Fragments from <i>P. troglodytes</i>, <i>G. gorilla</i>, <i>P. pygmaeus</i>, and <i>H. agilis</i>, respectively (108 and 22 bp instead of 130 bp).</p

Frequencies of the thrifty type amino acids in <i>ADRB2</i>, <i>ADRB3</i> and <i>PPARG</i> of non-human primates.

<p>Macaques are <i>M. mulatta</i>, <i>M. fuscata</i>, <i>M. fascicularis</i>, <i>M. nemestrina</i>, and <i>M. radiata</i>.</p>*<p>(<i>M. mulatta</i>, <i>M. fuscata</i> and <i>M. fascicularis</i>). ND:not detected.</p>**<p>Pima Indians.</p