Paprika extract as a natural antioxidant in cold-stored pork patties: Effect on oxidative stability and heterocyclic amines inhibition.

In this study, we compared the degree of oxidation of pork patties refrigerated at 7 °C for 0, 7, and 14 days and the content of 10 types of heterocyclic amines (HCAs) after heating. The pork patties used in the study were added with 0.7 mg sodium nitrite (SN) and 5 mg paprika extract (PE), respectively. IQx (2-Amino-3-methyl-imidazo[4,5-f]-quinoxaline), MeIQx (2-Amino-3, 8-dimethyl-imidazo[4,5-f]-quinoxaline), PhIP (2-Amino-1-methyl-6-phenyl-imidazo[4,5-b]-pyridine), and Harman (1-Methyl-9H-pyrido[4,3-b]-indole) contents increased with increasing storage periods of treatment. On the other hand, HCAs production in SN and PE treatments were suppressed over the storage period, with IQ (2-Amino-3-methyl-imidazo[4,5-f]-quinoline) and Aαc (2-Amino-9H-dipyrido[2,3-b]-indole) being suppressed significantly (P < 0.05). The control's pH, cooking loss, lipid, and protein oxidation were higher than SN and PE-treated patties at 14 d (P < 0.05). These differences affect the formation of HCAs. PLS-DA showed a strong correlation between protein oxidation and IQx, Harman, 4,8-DiMelQx (2-Amino-3, 4, 8-trimethyl-imidazo[4,5-f]-quinoxaline), PhIP, and MeIQx, while lipid oxidation correlated with IQx, Harman, and PhIP. Both SN and PE showed HCAs inhibitory activity and exhibited oxidative stability during storage.

Effect of Novel Polymer-Free Nitrogen-Doped Titanium Dioxide Film-Coated Coronary Stent Loaded With Mycophenolic Acid.

Background: Titanium is commonly used in blood-exposed medical devices because it has superior blood compatibility. Mycophenolic acid inhibits the proliferation of vascular smooth muscle cells. This study examined the effect of a non-polymer TiO2 thin film-coated stent with mycophenolic acid in a porcine coronary overstretch restenosis model. Methods: Thirty coronary arteries in 15 pigs were randomized into three groups in which the coronary arteries were treated with a TiO2 film-coated stent with mycophenolic acid (NTM, n = 10), everolimus-eluting stent with biodegradable polymer (EES, n = 10), or TiO2 film-coated stent (NT, n = 10). A histopathologic analysis was performed 28 days after the stenting. Results: There were no significant intergroup differences in injury score, internal elastic lamina area, or inflammation score. Percent area stenosis was significantly smaller in the NTM and EES groups than in the NT group (36.1 ± 13.63% vs. 31.6 ± 7.74% vs. 45.5 ± 18.96%, respectively, p = 0.0003). Fibrin score was greater in the EES group than in the NTM and NT groups [2.0 (range, 2.0-2.0) vs. 1.0 (range, 1.0-1.75) vs. 1.0 (range, 1.0-1.0), respectively, p < 0.0001]. The in-stent occlusion rate measured by micro-computed tomography demonstrated similar percent area stenosis rates on histology analysis (36.1 ± 15.10% in NTM vs. 31.6 ± 8.89% in EES vs. 45.5 ± 17.26% in NT, p < 0.05). Conclusion: The NTM more effectively reduced neointima proliferation than the NT. Moreover, the inhibitory effect of NTM on smooth muscle cell proliferation was not inferior to that of the polymer-based EES with lower fibrin deposition in this porcine coronary restenosis model.

Effect of Human or Mouse IL-7 on the Homeostasis of Porcine T Lymphocytes.

Due to the inconsistent fluctuation of blood supply for transfusion, much attention has been paid to the development of artificial blood using other animals. Although mini-pigs are candidate animals, contamination of mini-pig T cells in artificial blood may cause a major safety concern. Therefore, it is important to analyze the cross-reactivity of IL-7, the major survival factor for T lymphocytes, between human, mouse, and mini-pig. Thus, we compared the protein sequences of IL-7 and found that porcine IL-7 was evolutionarily different from human IL-7. We also observed that when porcine T cells were cultured with either human or mouse IL-7, these cells did not increase the survival or proliferation compared to negative controls. These results suggest that porcine T cells do not recognize human or mouse IL-7 as their survival factor.

Depletion of CLK2 sensitizes glioma stem-like cells to PI3K/mTOR and FGFR inhibitors.

The Cdc2-like kinases (CLKs) regulate RNA splicing and have been shown to suppress cell growth. Knockdown of CLK2 was found to block glioma stem-like cell (GSC) growth in vivo through the AKT/FOXO3a/p27 pathway without activating mTOR and MAPK signaling, suggesting that these pathways mediate resistance to CLK2 inhibition. We identified CLK2 binding partners using immunoprecipitation assays and confirmed their interactions in vitro in GSCs. We then tested the cellular viability of several signaling inhibitors in parental and CLK2 knockdown GSCs. Our results demonstrate that CLK2 binds to 14-3-3τ isoform and prevents its ubiquitination in GSCs. Stable CLK2 knockdown increased PP2A activity and activated PI3K signaling. Treatment with a PI3K/mTOR inhibitor in CLK2 knockdown cells led to a modest reduction in cell viability compared to drug treatment alone at a lower dose. However, FGFR inhibitor in CLK2 knockdown cells led to a decrease in cell viability and increased apoptosis. Reduced expression of CLK2 in glioblastoma, in combination with FGFR inhibitors, led to synergistic apoptosis induction and cell cycle arrest compared to blockade or either kinase alone.

Establishment and Characterization of Immortalized Miniature Pig Pancreatic Cell Lines Expressing Oncogenic K-RasG12D.

In recent decades, many studies on the treatment and prevention of pancreatic cancer have been conducted. However, pancreatic cancer remains incurable, with a high mortality rate. Although mouse models have been widely used for preclinical pancreatic cancer research, these models have many differences from humans. Therefore, large animals may be more useful for the investigation of pancreatic cancer. Pigs have recently emerged as a new model of pancreatic cancer due to their similarities to humans, but no pig pancreatic cancer cell lines have been established for use in drug screening or analysis of tumor biology. Here, we established and characterized an immortalized miniature pig pancreatic cell line derived from primary pancreatic cells and pancreatic cancer-like cells expressing K-rasG12D regulated by the human PTF1A promoter. Using this immortalized cell line, we analyzed the gene expression and phenotypes associated with cancer cell characteristics. Notably, we found that acinar-to-ductal transition was caused by K-rasG12D in the cell line constructed from acinar cells. This may constitute a good research model for the analysis of acinar-to-ductal metaplasia in human pancreatic cancer.

Prevalence and characterization of Clostridium perfringens isolated from feces of captive cynomolgus monkeys (Macaca fascicularis).

Clostridium perfringens is ubiquitous in the environment and the gastrointestinal tract of warm-blooded animals. While part of the gut microbiome, abnormal growth of C. perfringens causes histotoxic, neurologic, and enteric diseases in a variety of animal species, including humans, due to the production of toxins. There is extremely limited information on C. perfringens infection in non-human primates. Presently, 10 strains were successfully isolated from 126 monkeys and confirmed by molecular and biochemical analyses. All isolates were genotype A based on molecular analysis. Alpha toxin was identified in all isolates. Beta 2 toxin was detected in only three isolates. No other toxins, including enterotoxin, beta, iota, epsilon, and net B toxin, were identified in any isolate. All isolates were highly susceptible to ß-lactam antibiotics. Double hemolysis and lecithinase activity were commonly observed in all strains. Biofilm formation, which can increase antibiotic resistance, was identified in 90% of the isolates. The data are the first report the prevalence and characteristics of C. perfringens isolated from captive cynomolgus monkeys.

Chronic Infiltration of T Lymphocytes into the Brain in a Non-human Primate Model of Parkinson's Disease.

Study of interactions between the nervous system and immunity offers insights into the pathogenesis of Parkinson's disease (PD) and potential therapeutic strategies for neurodegenerative diseases. Studies on rodents have revealed regulatory mechanisms of microglial activation and T lymphocyte recruitment in PD. However, the mechanisms underlying chronic T lymphocyte infiltration into the brain after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injection into a non-human primate (NHP) model of PD remain unknown. This study aimed to investigate changes in serum RANTES (regulated on activation, normal T cell expression and secretion) and analyze the chronic infiltration of T lymphocytes into the brain and microglia activation in NHPs at 48 weeks post-MPTP administration. We found selective and local chronic infiltration of CD4+ and CD8+ T lymphocytes, loss of dopaminergic neurons, dopamine transporter expression, chronic normalization of RANTES in the peripheral blood, and altered microglial morphology at 48 weeks after MPTP injection. This study confirms the involvement of CD4+ and CD8+ T lymphocyte infiltration in MPTP-induced NHP models of PD. Additionally, we corroborated previous findings regarding the mechanisms of T lymphocyte-induced neurodegeneration. The findings of chronic infiltration of T lymphocytes in our NHP model of PD provide novel insights into PD pathogenesis and the development of preventive and therapeutic agents.

Idiopathic chronic diarrhea associated with dysbiosis in a captive cynomolgus macaque (Macaca fascicularis).

Chronic inflammatory enteric diseases occur commonly in humans and animals, especially in captive bred macaques. However, information about the etiology of idiopathic chronic inflammatory diarrhea in cynomolgus monkeys is limited. In this paper, we reported the unusual case of idiopathic chronic diarrhea in a captive cynomolgus monkey based on microbial, imaging, and microbiome examinations.

A pilot study on assessment of locomotor behavior using a video tracking system in minipigs.

Pigs are often selected for large animal models including for neuroscience and behavioral research, because their anatomy and biochemistry are similar to those of humans. However, behavioral assessments, in combination with objective long-term monitoring, is difficult. In this study, we introduced an automated video tracking system which was previously used in rodent studies, for use with pig models. Locomotor behaviors (total distance, number of zone transitions, and velocity) were evaluated and their changes were validated by different 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration methods and dosing regimens. Three minipigs (23-29 kg) received subcutaneous or intravenous MPTP, either 1 or 3 times per week. Immediately after MPTP injection, the minipigs remained in a corner and exhibited reduced trajectory. In addition, the total distance travelled, number of zone transitions, and velocity were greatly reduced at every MPTP administration in all the minipigs, accompanying to increased resting time. However, the MPTP-induced symptoms were reversed when MPTP administration was terminated. In conclusion, this automated video-tracking system was able to monitor long-term locomotor activity and differentiate detailed alterations in large animals. It has the advantages of being easy to use, higher resolution, less effort, and more delicate tracking. Additionally, as our method can be applied to the animals' home pen, no habituation is needed.

Embryo aggregation regulates in vitro stress conditions to promote developmental competence in pigs.

Embryo aggregation is a useful method to produce blastocysts with high developmental competence to generate more offspring in various mammals, but the underlying mechanism(s) regarding the beneficial effects are largely unknown. In this study, we investigated the effects of embryo aggregation using 4-cell stage embryos in in vitro developmental competence and the relationship of stress conditions in porcine early embryogenesis. We conducted aggregation using the well of the well system and confirmed that aggregation using two or three embryos was useful for obtaining blastocysts. Aggregated embryos significantly improved developmental competence, including blastocyst formation rate, blastomere number, ICM/TE ratio, and cellular survival rate, compared to non-aggregated embryos. Investigation into the relationship between embryo aggregation and stress conditions revealed that mitochondrial function increased, and oxidative and endoplasmic reticulum (ER)-stress decreased compared to 1X (non-aggregated embryos) blastocysts. In addition, 3X (three-embryo aggregated) blastocysts increased the expression of pluripotency, anti-apoptosis, and implantation related genes, and decreased expression of pro-apoptosis related genes. Therefore, these findings indicate that embryo aggregation regulates in vitro stress conditions to increase developmental competence and contributes to the in vitro production of high-quality embryos and the large-scale production of transgenic and chimeric pigs.

Transient meiotic arrest maintained by DON (6-diazo-5-oxo-l-norleucine) enhances nuclear/cytoplasmic maturation of porcine oocytes.

The developmental competence of in vitro-matured oocytes is still lower than that of the in vivo-matured oocytes due to precocious meiotic resumption and inappropriate cytoplasmic maturation. Although numerous efforts have been attempted to accomplish better in vitro maturation (IVM) condition, only limited progress has been achieved. Thus, a current study was conducted to examine the effects of 6-diazo-5-oxo-l-norleucine (DON, an inhibitor of hyaluronan synthesis) during the first half period of IVM on nuclear/cytoplasmic maturation of porcine oocytes and subsequent embryonic development. Based on the observation of the nucleus pattern, metaphase II (MII) oocyte production rate in 1 µM DON group was significantly higher than other groups at 44 h of IVM. The 1 µM of DON was suggested to be optimal for porcine IVM and was therefore used for further investigation. Meiotic arrest effect of DON was maximal at 6 h of IVM, which was supported by the maintenance of significantly higher intra-oocyte cAMP level. In addition, increased pERK1/2 levels and clear rearrangement of cortical granules in membrane of MII oocytes matured with DON provided the evidence for balanced meiosis progression between nuclear and cytoplasmic maturation. Subsequently, DON significantly improved blastocyst formation rate, total cell numbers, and cellular survival in blastocysts after parthenogenetic activation, in vitro fertilization, and somatic cell nuclear transfer. Altogether, our results showed for the first time that 1 µM DON can be used to increase the yield of developmentally competent MII oocytes by synchronizing nuclear/cytoplasmic maturation, and it subsequently improves embryo developmental competence.

Increased CD68/TGFß Co-expressing Microglia/ Macrophages after Transient Middle Cerebral Artery Occlusion in Rhesus Monkeys.

The function of microglia/macrophages after ischemic stroke is poorly understood. This study examines the role of microglia/macrophages in the focal infarct area after transient middle cerebral artery occlusion (MCAO) in rhesus monkeys. We measured infarct volume and neurological function by magnetic resonance imaging (MRI) and non-human primate stroke scale (NHPSS), respectively, to assess temporal changes following MCAO. Activated phagocytic microglia/macrophages were examined by immunohistochemistry in post-mortem brains (n=6 MCAO, n=2 controls) at 3 and 24 hours (acute stage), 2 and 4 weeks (subacute stage), and 4, and 20 months (chronic stage) following MCAO. We found that the infarct volume progressively decreased between 1 and 4 weeks following MCAO, in parallel with the neurological recovery. Greater presence of cluster of differentiation 68 (CD68)-expressing microglia/macrophages was detected in the infarct lesion in the subacute and chronic stage, compared to the acute stage. Surprisingly, 98~99% of transforming growth factor beta (TGFß) was found co-localized with CD68-expressing cells. CD68-expressing microglia/macrophages, rather than CD206+ cells, may exert anti-inflammatory effects by secreting TGFß after the subacute stage of ischemic stroke. CD68+ microglia/macrophages can therefore be used as a potential therapeutic target.

Abnormal Mitochondria in a Non-human Primate Model of MPTP-induced Parkinson's Disease: Drp1 and CDK5/p25 Signaling.

Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD. Here, we investigated the balance between mitochondrial fusion and fission in the substantia nigra of a non-human primate model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. We found that MPTP induced shorter and abnormally distributed mitochondria. This phenomenon was accompanied by the activation of dynamin-related protein 1 (Drp1), a mitochondrial fission protein, through increased phosphorylation at S616. Thereafter, we assessed for activation of the components of the cyclin-dependent kinase 5 (CDK5) and extracellular signal-regulated kinase (ERK) signaling cascades, which are known regulators of Drp1(S616) phosphorylation. MPTP induced an increase in p25 and p35, which are required for CDK5 activation. Together, these findings suggest that the phosphorylation of Drp1(S616) by CDK5 is involved in mitochondrial fission in the substantia nigra of a non-human primate model of MPTP-induced PD.

Rise of the Visible Monkey: Sectioned Images of Rhesus Monkey.

BACKGROUND: Gross anatomy and sectional anatomy of a monkey should be known by students and researchers of veterinary medicine and medical research. However, materials to learn the anatomy of a monkey are scarce. Thus, the objective of this study was to produce a Visible Monkey data set containing cross sectional images, computed tomographs (CTs), and magnetic resonance images (MRIs) of a monkey whole body. METHODS: Before and after sacrifice, a female rhesus monkey was used for 3 Tesla MRI and CT scanning. The monkey was frozen and sectioned at 0.05 mm intervals for the head region and at 0.5 mm intervals for the rest of the body using a cryomacrotome. Each sectioned surface was photographed using a digital camera to obtain horizontal sectioned images. Segmentation of sectioned images was performed to elaborate three-dimensional (3D) models of the skin and brain. RESULTS: A total of 1,612 horizontal sectioned images of the head and 1,355 images of the remaining region were obtained. The small pixel size (0.024 mm × 0.024 mm) and real color (48 bits color) of these images enabled observations of minute structures. CONCLUSION: Due to small intervals of these images, continuous structures could be traced completely. Moreover, 3D models of the skin and brain could be used for virtual dissections. Sectioned images of this study will enhance the understanding of monkey anatomy and foster further studies. These images will be provided to any requesting researcher free of charge.

Draft Genome Sequence of Atopobacter sp. Strain AH10, Isolated from a Vaginal Swab from Macaca fascicularis.

A bacterial strain belonging to the genus Atopobacter was isolated from a vaginal swab from a crab-eating macaque (Macaca fascicularis). Here, we report the draft genome sequence of this strain, AH10.

Reference values of hematological and biochemical parameters in young-adult cynomolgus monkey (Macaca fascicularis) and rhesus monkey (Macaca mulatta) anesthetized with ketamine hydrochloride.

Nonhuman primate models are valuable in biomedical research. However, reference data for clinical pathology parameters in cynomolgus and rhesus monkeys are limited. In the present study, we established hematologic and biochemical reference intervals for healthy cynomolgus and rhesus monkeys anesthetized with ketamine hydrochloride. A total of 142 cynomolgus monkeys (28 males and 114 females) and 42 rhesus monkeys (22 males and 20 females) were selected and analyzed in order to examine reference intervals of 20 hematological and 16 biochemical parameters. The effects of sex were also investigated. Reference intervals for hematological and biochemical parameters were separately established by species (cynomolgus and rhesus) and sex (male and female). No sex-related differences were determined in erythrocyte-related parameters for cynomolgus and rhesus monkey housed in indoor laboratory conditions. Alkaline phosphatase and gamma glutamyltransferase were significantly lower in females than males in both cynomolgus and rhesus monkeys aged 48-96 months. The reference values for hematological and biochemical parameters established herein might provide valuable information for researchers using cynomolgus and rhesus monkeys in experimental conditions for biomedical studies.

Enhanced neutralizing antibody response induced by inactivated enterovirus 71 in cynomolgus monkeys.

Enterovirus 71 (EV71) is a major etiological agent of various public health issues, particularly in the Asia-Pacific region. EV71 causes hand-foot-and-mouth disease (HFMD) and is associated with serious neurological disorders in young children. A formalin-inactivated EV71 candidate vaccine (KCDC-HFMDV1-EV71) based on the C4 subgenotype was previously developed and confirmed to be a potential candidate vaccine for prevention of EV71 infection in mice. In this study, an inactivated EV71 vaccine was used for analysis of long-term immunogenicity and efficacy in cynomolgus monkeys, a common nonhuman primate model. The vaccine was immunized three times at 0, 4, and 8 weeks with either 20-µg doses of EV71 candidate vaccine formulated with aluminum hydroxide gel adjuvant or phosphate-buffered saline as a control. The group immunized with the inactivated EV71 showed significantly increased EV71-specific antibody and serum neutralizing antibody titers at 3 weeks after vaccination and maintained these elevated titers until the end of the experiment (54 weeks after vaccination). The sera from vaccinated cynomolgus monkeys showed a crossreactive neutralizing antibody response to the heterologous subtype of EV71 (B1-4, C1, and C2). These findings suggest that the inactivated EV71 candidate vaccine may be a potential vaccine candidate and valuable tool for the control of HFMD.

The effects of kinase modulation on in vitro maturation according to different cumulus-oocyte complex morphologies.

Successful production of transgenic pigs requires oocytes with a high developmental competence. However, cumulus-oocyte complexes (COCs) obtained from antral follicles have a heterogeneous morphology. COCs can be classified into one of two classes: class I, with five or more layers of cumulus cells; and class II, with one or two layers of cumulus cells. Activator [e.g., epidermal growth factor (EGF)] or inhibitors (e.g., wortmannin and U0126) are added to modulate kinases in oocytes during meiosis. In the present study, we investigated the effects of kinase modulation on nuclear and cytoplasmic maturation in COCs. Class I COCs showed a significantly higher developmental competence than class II COCs. Moreover, the expression of two kinases, AKT and ERK, differed between class I and class II COCs during in vitro maturation (IVM). Initially, inhibition of the PI3K/AKT signaling pathway in class I COCs during early IVM (0-22 h) decreased developmental parameters, such as blastocyst formation rate, blastomere number, and cell survival. Conversely, EGF-mediated AKT activation in class II COCs enhanced developmental capacity. Regarding the MAPK signaling pathway, inhibition of ERK by U0126 in class II COCs during early IVM impaired developmental competence. However, transient treatment with U0126 in class II COCs increased oocyte maturation and AKT activity, improving embryonic development. Additionally, western blotting showed that inhibition of ERK activity negatively regulated the AKT signaling pathway, indicative of a relationship between AKT and MAPK signaling in the process underlying meiotic progression in pigs. These findings may help increase the developmental competence and utilization rate of pig COCs with regard to the production of transgenic pigs and improve our understanding of kinase-associated meiosis events.

In vivo study of paraspinal muscle weakness using botulinum toxin in one primate model.

BACKGROUND: It has been generally speculated that paraspinal muscle weakness is related to the spinal degeneration including intervertebral disc failure. The purpose of this study was to investigate the effects of paraspinal muscle weakness induced by the botulinum toxin type-A on the lumbar spine and behavior pattern in an in-vivo primate model which has an upright locomotion similar to that of humans. METHODS: Botox injections into paraspinal muscle of one cynomolgus monkey were conducted biweekly up to 19 weeks at L2-L3, L3-L4 and L4-L5. MRIs were performed for measurement of muscle cross-sectional areas and behavioral data were collected using a high-resolution portable digital video camera. FINDINGS: The cross-sectional areas of the paraspinal muscles at L2-L3, L3-L4 and L4-L5 decreased by 8%, 12% and 8% at 21 weeks after the Botox injection, respectively. Intervertebral disc thickness at L2-L3, L3-L4 and L4-L5 decreased by 6%, 8% and 5% at 21 weeks after initial Botox injection, respectively. After the Botox injections, locomotion and movement activity of the monkey was decreased. The duration of sitting increased from 21% to a maximum of 97% at 9 weeks after the Botox injection, while stance time decreased from 9% to a minimum of 1% at 11 weeks post Botox injection. INTERPRETATION: The findings of this study revealed that paraspinal muscle atrophy affects intervertebral disc morphology and locomotion activity of a primate and may lead to an onset of intervertebral disc degeneration.

Identification and characterization of the tyrosinase gene (TYR) and its transcript variants (TYR_1 and TYR_2) in the crab-eating macaque (Macaca fascicularis).

Tyrosinase is a copper-containing enzyme that regulates melanin biosynthesis and is encoded by the tyrosinase (TYR) gene. Previous studies demonstrated that mutations in TYR could lead to oculocutaneous albinism type 1 (OCA1) owing to the failure of melanin formation. Although a previous study found that albinism in the rhesus monkey was derived from a mutation in TYR, the identification and characterization of this gene in non-human primates has not been achieved thus far. Thus, using the rapid amplification of cDNA ends (RACE) and internal reverse transcription PCR (RT-PCR) we identified the full-length sequence of TYR in the crab-eating macaque, and two different transcript variants (TYR_1 and TYR_2). While TYR_1 comprised five exons and its coding sequence was highly similar to that of humans, TYR_2 comprised four exons and was generated by a third-exon-skipping event. Interestingly, these two transcripts were also present in the African green monkey (Old World monkey) and the common marmoset (New World monkey). Deduced amino acid sequence analyses revealed that TYR_2 had a shorter C-terminal region than TYR_1 owing to the exon-skipping event. Thus, the present study is the first to identify and characterize a full-length TYR gene in a non-human primate, while the further validation of the third-exon-skipping in TYR indicates that this event is well conserved in the primate lineage. Therefore, this study provides useful and important information for the study of albinism using non-human primate models.