Christian R. Abee

Molecular Genetics of Spectral Tuning in New World Monkey Color Vision

Abstract. Although most New World monkeys have only one X-linked photopigment locus, many species have three polymorphic alleles at the locus. The three alleles in the squirrel monkey and capuchin have spectral peaks near 562, 550, and 535 nm, respectively, and the three alleles in the marmoset and tamarin have spectral peaks near 562, 556, and 543 nm, respectively. To determine the amino acids responsible for the spectral sensitivity differences among these pigment variants, we sequenced all exons of the three alleles in each of these four species. From the deduced amino acid sequences and the spectral peak information and from previous studies of the spectral tuning of X-linked pigments in humans and New World monkeys, we estimated that the Ala → Ser, Ile → Phe, Gly → Ser, Phe → Tyr, and Ala → Tyr substitutions at residue positions 180, 229, 233, 277, and 285, respectively, cause spectral shifts of about 5, −2, −1, 8, and 15 nm. On the other hand, the substitutions His → Tyr, Met → Val or Leu, and Ala → Tyr at positions 116, 275, and 276, respectively, have no discernible spectral tuning effect, though residues 275 and 276 are inside the transmembrane domains. Many substitutions between Val and Ile or between Val and Ala have occurred in the transmembrane domains among the New World monkey pigment variants but apparently have no effect on spectral tuning. Our study suggests that, in addition to amino acid changes involving a hydroxyl group, large changes in residue size can also cause a spectral shift in a visual pigment.

Medical Care and Management of the Squirrel Monkey

The use of the squirrel monkey in biomedical research has helped to improve our understanding of many diseases and other disorders of human beings in the past 20 years. Most of this research has been and continues to be carried out using animals that are captured as juveniles or adults from the wild. The introduction and long-term maintenance of these animals in the laboratory requires an understanding of the husbandry and medical care needs of this species. With improvements in facility design, husbandry techniques, and equipment for medical care, morbidity and mortality among laboratory-housed squirrel monkeys have been greatly reduced. An excellent chapter on the care and management of the squirrel monkey was written by Lang (1968) and is a valuable source of additional information on the care of the squirrel monkey.

The squirrel monkey as an animal model of pelvic relaxation: An evaluation of a large breeding colony

OBJECTIVE Findings of pelvic relaxation have been reported in up to 50% of older adult female squirrel monkeys. To evaluate further the potential use of the squirrel monkey as an animal model of pelvic relaxation, we objectively observed and described the perineal findings of 160 adult females. The aim of this study was to examine the relationship of perineal findings to age and parity, factors thought to predispose women to pelvic relaxation. STUDY DESIGN The urethra, cervix, and anterior and posterior segments of the vagina were evaluated. The degree of support loss at each site was documented. Genital measurements were obtained by previously reported methods. The findings were tested for association with elements of obstetric history, age, and subspecies. RESULTS The females represented three subspecies and ranged from 3 to 17 years old with parities of 0 to 10. The proportion of females with normal support was inversely related to increasing parity and age. Although birth weights, frequency of dystocia at term, and requirement for cesarean section did not differ significantly between females with and without evidence of prolapse, animals with multiple sites of prolapse tended to have infants with higher birth weights. Animals without prolapse were significantly younger and less likely to have been delivered of a term infant (p < 0.001). Subspecies differences unrelated to age or parity were found for each of the genital measurements. Differences were also found between animals with normal perineal findings and those with findings of prolapse. Animals with prolapse had shorter perineal bodies (p < 0.001), greater genital hiatal ratios (p < 0.001), and wider genital hiatal measurements (p < 0.001). Females with abnormal pelvic findings were of increased parity (4.0 vs 1.6, p < 0.001) and age (9.4 vs 6.3 years, p < 0.001) compared with those normal pelvic findings. CONCLUSION Analysis of genital prolapse in a large population of breeding squirrel monkeys demonstrated an association of loss of pelvic support with age and parity. A tendency for loss of support at multiple sites was associated with obstetric complications. These observations support continuing investigation into the nature and cause of spontaneous pelvic relaxation in this species and support the potential use of this nonhuman primate as an animal model.

Cerebrovascular amyloidosis in squirrel monkeys and rhesus monkeys: Apolipoprotein E genotype

Some neuropathological changes characteristic of aging and Alzheimers disease (AD) in humans are present also in senescent non‐human primates. The human apoE4 allele is associated with an increased risk of developing late‐onset familial and sporadic AD. We found that rhesus monkeys and three subspecies of squirrel monkeys are homozygous for apoE phenotype with arginine at positions 112 and 158 as in human apoE4. However, in both species threonine replaces arginine at position 61 of human apoE. It was previously shown that arginine 61 was critical in determining apoE4 lipoprotein distribution in humans.

Biochemical genetic markers of squirrel monkeys and their use for pedigree validation

Family data for 14 biochemical genetic markers of squirrel monkeys (genusSaimiri) were derived from 73 pedigreed progeny and both parents of each, as well as from 16 additional progeny and one parent of each. The data for each marker and the phenotypic patterns were consistent with autosomal codominant inheritance. It was concluded from the genetic marker data that the pedigree records of seven progeny were incorrect. Retrospective investigations of colony records followed by typing of animals that might possibly have been a parent enabled five of the pedigree records to be corrected. Although five of the pedigree errors were cases of mistaken paternity, the other two apparently were the consequence of infant swapping between dams shortly after birth. Because squirrel monkeys exhibit a high degree of allomaternal behavior, infant swapping between dams may occur more frequently than in many other nonhuman primate species.

Obesity Related Alterations in Plasma Cytokines and Metabolic Hormones in Chimpanzees

Obesity is characterized by chronic low-grade inflammation and serves as a major risk factor for hypertension, coronary artery disease, dyslipidemias, and type-2 diabetes. The purpose of this study was to examine changes in metabolic hormones, inflammatory cytokines, and immune function, in lean, overweight, and obese chimpanzees in a controlled environment. We observed increased plasma circulating levels of proinflammatory TH-1 cytokines, Interferon gamma, interleukin-6, interleukin-12p40, tumor necrosis factor, soluble CD40 ligand, and Interleukin-1β and anti-inflammatory TH-2 cytokines, Interleukin-4, Interleukin-RA, Interleukin-10, and Interleukin-13 in overweight and obese chimpanzees. We also observed increased levels of metabolic hormones glucagon-like-peptide-1, glucagon, connecting peptide, insulin, pancreatic peptide YY3–36, and leptin in the plasma of overweight and obese chimpanzees. Chemokine, eotaxin, fractalkine, and monocyte chemoattractant protein-1 were higher in lean compared to obese chimpanzees, while chemokine ligand 8 increased in plasma of obese chimpanzees. We also observed an obesity-related effect on immune function as demonstrated by lower mitogen induced proliferation, and natural killer activity and higher production of IFN-γ by PBMC in Elispot assay, These findings suggest that lean, overweight, and obese chimpanzees share circulating inflammatory cytokines and metabolic hormone levels with humans and that chimpanzees can serve as a useful animal model for human studies.

The normal and abnormal owl monkey (Aotus sp.) heart: Looking at cardiomyopathy changes with echocardiography and electrocardiography

Background  Cardiovascular disease, especially cardiomyopathy, was the major cause of death among owl monkeys (Aotus sp.) at a major colony and threatened colony sustainability. For this study, echocardiography (echo) and electrocardiography (ECG) normal values were established, and cardiomyopathy animals identified.

Ultrasound-guided follicular aspiration in squirrel monkeys

The objective of this study was to test whether ultrasound‐guided oocyte retrieval is an effective mechanism for collecting oocytes in squirrel monkeys. Although ultrasound‐guided follicular aspiration has been described in Old World primates, oocyte retrieval in New World primates is typically performed via laparoscopy or laparotomy. However, these procedures, especially the first, can be invasive. Ultrasound has been used for pregnancy monitoring in multiple species of primates including Saimiri spp. Transabdominal ultrasound as a diagnostic tool is non‐invasive. Transabdominal ultrasound was utilized to visualize ovarian follicles during aspiration under light anesthesia. This procedure resulted in collection of a total of 29 oocytes from six animals with minimal post‐procedural pain. Manipulated animals were returned to the social group the same day.

Experimental Zika Virus Infection of Neotropical Primates

The establishment of a sylvatic reservoir of Zika virus (ZIKV) in the Americas is dependent on the susceptibility of primates of sufficient population density, the duration and magnitude of viremia, and their exposure to the human mosquito-borne transmission cycle. To assess the susceptibility of squirrel (Saimiri sp.) and owl monkeys (Aotus sp.) to infection, we inoculated four animals of each species with ZIKV from the current epidemic. Viremia in the absence of detectible disease was observed in both species and seroconversion occurred by day 28. ZIKV was detected in the spleen of three owl monkeys: one at 7 days postinoculation (dpi) and two at 14 dpi. This study confirms the susceptibility to ZIKV infection of two Neotropical primate species that live in close proximity to humans in South America, suggesting that they could support a widespread sylvatic ZIKV cycle there. Collectively, establishment of a ZIKV sylvatic transmission cycle in South America would imperil eradication efforts and could provide a mechanism for continued exposure of humans to ZIKV infection and disease.

Low oxygen inhibits but complex high-glucose medium facilitates in vitro maturation of squirrel monkey oocyte-granulosa cell complexes

Purpose:The objectives of these in vitro maturation studies in primate cumulus-oocyte complexes (COCs) were to evaluate the effect of a reduced-oxygen environment and to compare medium with a high-glucose concentration to medium with pyruvate but no glucose.Methods:COCs were retrieved from squirrel monkeys stimulated with 1 mg of follicle-stimulating hormone (FSH) for 4–6 days. Experiment 1 examined maturation after 48 hr in 5% O2/5% CO2/90% N2compared with 5% CO2/air. The medium was CMRL-1066 containing moderate glucose (5.5 mM) supplemented with 1 mM glutamine, 0.33 mM pyruvate, 0.075 IU/ml human FSH, 5 IU/ml human chorionic gonadotropin, 75 U penicillin G/ml, and 20% fetal bovine serum. Experiment 2 in 5% CO2/air, compared P-l medium (pyruvate and lactate but no glucose) to Waymouths medium (27.5 mM glucose), both with identical supplements.Results:Only 3 (8%) of 37 COCs matured in 5% O2, while 39 (49%) of 80 matured in ambient O2. Fourteen (22%) of 64 complexes matured in P-1 medium, compared to 47 (49%) of 96 meiosis II oocytes in Waymouths medium (P < 0.05).Conclusions:These are the first primate studies showing detrimental effects of reduced-oxygen culture on in vitro maturation. Additionally, maturation was enhanced with complex high-glucose medium suggesting that the predominant metabolism is aerobic glycolysis.