Primates Research Articles

Animal models for partial heart transplantation.

Partial heart transplantation delivers growing heart valve implants by transplanting the part of the heart containing the necessary heart valve only. In contrast to heart transplantation, partial heart transplantation spares the native ventricles. This has important implications for partial heart transplant biology, including the allowable ischemia time, optimal graft preservation, primary graft dysfunction, immune rejection, and optimal immunosuppression. Exploration of partial heart transplant biology will depend on suitable animal models. Here we review our experience with partial heart transplantation in rodents, piglets, and non-human primates. This review is based on our experience with partial heart transplantation using over 100 rodents, over 50 piglets and one baboon. Suitable animal models for partial heart transplantation include rodent heterotopic partial heart transplantation, piglet orthotopic partial heart transplantation, and non-human primate partial heart xenotransplantation. Rodent models are relatively cheap and offer extensive availability of research tools. However, rodent open-heart surgery is technically not feasible. This limits rodents to heterotopic partial heart transplant models. Piglets are comparable in size to children. This allows for open-heart surgery using clinical grade equipment for orthoptic partial heart transplantation. Piglets also grow rapidly, which is useful for studying partial heart transplant growth. Finally, nonhuman primates are immunologically most closely related to humans. Therefore, nonhuman primates are most suitable for studying partial heart transplant immunobiology and xenotransplantation. Animal research is a privilege that is contingent on utilitarian ethics and the 3R principles of replacement, reduction and refinement. This privilege allows the research community to seek fundamental knowledge about partial heart transplantation, and to apply this knowledge to enhance the health of children who require partial heart transplants.

Characterization of the genetic variation and evolutionary divergence of the CLEC18 family.

The C-type lectin family 18 (CLEC18) with lipid and glycan binding capabilities is important to metabolic regulation and innate immune responses against viral infection. However, human CLEC18 comprises three paralogous genes with highly similar sequences, making it challenging to distinguish genetic variations, expression patterns, and biological functions of individual CLEC18 paralogs. Additionally, the evolutionary relationship between human CLEC18 and its counterparts in other species remains unclear. To identify the sequence variation and evolutionary divergence of human CLEC18 paralogs, we conducted a comprehensive analysis using various resources, including human and non-human primate reference genome assemblies, human pangenome assemblies, and long-read-based whole-genome and -transcriptomesequencing datasets. We uncovered paralogous sequence variants (PSVs) and polymorphic variants (PVs) of human CLEC18 proteins, and identified distinct signatures specific to each CLEC18 paralog. Furthermore, we unveiled a novel segmental duplication for human CLEC18A gene. By comparing CLEC18 across human and non-human primates, our research showed that the CLEC18 paralogy probably occurred in the common ancestor of human and closely related non-human primates, and the lipid-binding CAP/SCP/TAPS domain of CLEC18 is more diverse than its glycan-binding CTLD. Moreover, we found that certain amino acids alterations at variant positions are exclusive to human CLEC18 paralogs. Our findings offer a comprehensive profiling of the intricate variations and evolutionary characteristics of human CLEC18.

A replicating RNA vaccine confers protection in a rhesus macaque model of Crimean-Congo hemorrhagic fever

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne febrile illness with a wide geographic distribution. In recent years the geographic range of Crimean-Congo hemorrhagic fever virus (CCHFV) and its tick vector have increased, placing an increasing number of people at risk of CCHFV infection. Currently, there are no widely available vaccines, and although the World Health Organization recommends ribavirin for treatment, its efficacy is unclear. Here we evaluate a promising replicating RNA vaccine in a rhesus macaque (Macaca mulatta) model of CCHF. This model provides an alternative to the established cynomolgus macaque model and recapitulates mild-to-moderate human disease. Rhesus macaques infected with CCHFV consistently exhibit viremia, detectable viral RNA in a multitude of tissues, and moderate pathology in the liver and spleen. We used this model to evaluate the immunogenicity and protective efficacy of a replicating RNA vaccine. Rhesus macaques vaccinated with RNAs expressing the CCHFV nucleoprotein and glycoprotein precursor developed robust non-neutralizing humoral immunity against the CCHFV nucleoprotein and had significant protection against the CCHFV challenge. Together, our data report a model of CCHF using rhesus macaques and demonstrate that our replicating RNA vaccine is immunogenic and protective in non-human primates after a prime-boost immunization.

Human musical capacity and products should have been induced by the hominin-specific combination of several biosocial features: A three-phase scheme on socio-ecological, cognitive, and cultural evolution.

Various selection pressures have shaped human uniqueness, for instance, music. When and why did musical universality and diversity emerge? Our hypothesis is that "music" initially originated from manipulative calls with limited musical elements. Thereafter, vocalizations became more complex and flexible along with a greater degree of social learning. Finally, constructed musical instruments and the language faculty resulted in diverse and context-specific music. Music precursors correspond to vocal communication among nonhuman primates, songbirds, and cetaceans. To place this scenario in hominin history, a three-phase scheme for music evolution is presented herein. We emphasize (1) the evolution of sociality and life history in australopithecines, (2) the evolution of cognitive and learning abilities in early/middle Homo, and (3) cultural evolution, primarily in Homo sapiens. Human musical capacity and products should be due to the hominin-specific combination of several biosocial features, including bipedalism, stable pair bonding, alloparenting, expanded brain size, and sexual selection.

Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates.

Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to HIV and other pathogens. However, antibody-antigen recognition is typically dominated by heavy chain complementarity determining region 3 (HCDR3) interactions, and vaccine priming of HCDR3-dominant bnAbs by germline-targeting immunogens has not been demonstrated in humans or outbred animals. In this work, immunization with N332-GT5, an HIV envelope trimer designed to target precursors of the HCDR3-dominant bnAb BG18, primed bnAb-precursor B cells in eight of eight rhesus macaques to substantial frequencies and with diverse lineages in germinal center and memory B cells. We confirmed bnAb-mimicking, HCDR3-dominant, trimer-binding interactions with cryo-electron microscopy. Our results demonstrate proof of principle for HCDR3-dominant bnAb-precursor priming in outbred animals and suggest that N332-GT5 holds promise for the induction of similar responses in humans.

TRIM37 is a primate-specific E3 ligase for Huntingtin and accounts for the striatal degeneration in Huntington's disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by preferential neuronal loss in the striatum. The mechanism underlying striatal selective neurodegeneration remains unclear, making it difficult to develop effective treatments for HD. In the brains of nonhuman primates, we examined the expression of Huntingtin (HTT), the gene responsible for HD. We found that HTT protein is highly expressed in striatal neurons due to its slow degradation in the striatum. We also identified tripartite motif-containing 37 (TRIM37) as a primate-specific protein that interacts with HTT and is selectively reduced in the primate striatum. TRIM37 promotes the ubiquitination and degradation of mutant HTT (mHTT) in vitro and modulates mHTT aggregation in mouse and monkey brains. Our findings suggest that nonhuman primates are crucial for understanding the mechanisms of human diseases such as HD and support TRIM37 as a potential therapeutic target for treating HD.

Landscape drives zoonotic malaria prevalence in non-human primates.

Zoonotic disease dynamics in wildlife hosts are rarely quantified at macroecological scales due to the lack of systematic surveys. Non-human primates (NHPs) host Plasmodium knowlesi, a zoonotic malaria of public health concern and the main barrier to malaria elimination in Southeast Asia. Understanding of regional P. knowlesi infection dynamics in wildlife is limited. Here, we systematically assemble reports of NHP P. knowlesi and investigate geographic determinants of prevalence in reservoir species. Meta-analysis of 6322 NHPs from 148 sites reveals that prevalence is heterogeneous across Southeast Asia, with low overall prevalence and high estimates for Malaysian Borneo. We find that regions exhibiting higher prevalence in NHPs overlap with human infection hotspots. In wildlife and humans, parasite transmission is linked to land conversion and fragmentation. By assembling remote sensing data and fitting statistical models to prevalence at multiple spatial scales, we identify novel relationships between P. knowlesi in NHPs and forest fragmentation. This suggests that higher prevalence may be contingent on habitat complexity, which would begin to explain observed geographic variation in parasite burden. These findings address critical gaps in understanding regional P. knowlesi epidemiology and indicate that prevalence in simian reservoirs may be a key spatial driver of human spillover risk.

Landscape drives zoonotic malaria prevalence in non-human primates

Zoonotic disease dynamics in wildlife hosts are rarely quantified at macroecological scales due to the lack of systematic surveys. Non-human primates (NHPs) host Plasmodium knowlesi, a zoonotic malaria of public health concern and the main barrier to malaria elimination in Southeast Asia. Understanding of regional P. knowlesi infection dynamics in wildlife is limited. Here, we systematically assemble reports of NHP P. knowlesi and investigate geographic determinants of prevalence in reservoir species. Meta-analysis of 6322 NHPs from 148 sites reveals that prevalence is heterogeneous across Southeast Asia, with low overall prevalence and high estimates for Malaysian Borneo. We find that regions exhibiting higher prevalence in NHPs overlap with human infection hotspots. In wildlife and humans, parasite transmission is linked to land conversion and fragmentation. By assembling remote sensing data and fitting statistical models to prevalence at multiple spatial scales, we identify novel relationships between P. knowlesi in NHPs and forest fragmentation. This suggests that higher prevalence may be contingent on habitat complexity, which would begin to explain observed geographic variation in parasite burden. These findings address critical gaps in understanding regional P. knowlesi epidemiology and indicate that prevalence in simian reservoirs may be a key spatial driver of human spillover risk.

Cardiac differentiation of chimpanzee induced pluripotent stem cell lines with different subspecies backgrounds.

The comparative analysis between humans and non-human primates is an instrumental approach for elucidating the evolutional traits and disease propensity of humans. However, in primates, cross-species analyses of their developmental events have encountered constraints because of the ethical and technical limitations in available sample collection, sequential monitoring, and manipulations. In an endeavor to surmount these challenges, in recent years, induced pluripotent stem cells (iPSCs) have garnered escalating interest as an in vitro tool for cross-species analyses between humans and non-human primates. Meanwhile, compared to humans, there is less information on in vitro differentiation of non-human primate iPSCs, and their genetic diversity including subspecies may cause different eligibility to in vitro differentiation methods. Therefore, antecedent to embarking on a comparative analysis to humans, it is a prerequisite to develop the efficacious methodologies for in vitro differentiation regardless of the intraspecies genetic background in non-human primates. In this study, we executed the in vitro differentiation of cardiomyocytes from four chimpanzee iPSC lines with different subspecies and individual backgrounds. To induce cardiomyocytes from chimpanzee iPSCs, we evaluated our methodology for in vitro cardiac differentiation of human iPSCs. Eventually, with minor alterations, our cardiac differentiation method was applicable to all chimpanzee iPSC lines tested as assessed by the expression of cardiac marker genes and the beating ability. Hence, our in vitro differentiation method will advance iPSC-based research of chimpanzee cardiac development and also hold possible utility to cross-species analyses among primate species.

Human MuStem cells are competent to fuse with nonhuman primate myofibers in a clinically relevant transplantation context: A proof-of-concept study.

We previously reported that human muscle-derived stem cells (hMuStem cells) contribute to tissue repair after local administration into injured skeletal muscle or infarcted heart in immunodeficient rodent models. However, extrapolation of these findings to a clinical context is problematic owing to the considerable differences often seen between in vivo findings in humans versus rodents. Therefore, we investigated whether the muscle regenerative behavior of hMuStem cells is maintained in a clinically relevant transplantation context. Human MuStem cells were intramuscularly administered by high-density microinjection matrices into nonhuman primates receiving tacrolimus-based immunosuppression thereby reproducing the protocol that has so far produced the best results in clinical trials of cell therapy in myopathies. Four and 9 weeks after administration, histological analysis of cell injection sites revealed large numbers of hMuStem cell-derived nuclei in all cases. Most graft-derived nuclei were distributed in small myofiber groups in which no signs of a specific immune response were observed. Importantly, hMuStem cells contributed to simian tissue repair by fusing mainly with host myofibers, demonstrating their capacity for myofiber regeneration in this model. Together, these findings obtained in a valid preclinical model provide new insights supporting the potential of hMuStem cells in future cell therapies for muscle diseases.

Prevalence of Upper Limb Length Discrepancy among Asymptomatic Population of Medical Students in Nepal: A Descriptive Cross Sectional Study

INTRODUCTIONUpper limb length discrepancy are frequently documented in various anatomical orthopedics and anthropometric journals. Proper idea about discrepancy is pivotal prior to any limb lengthening surgery. The aim of the study is to find out the prevalence of upper limb length discrepancy among asymptomatic population in medical students of Nepal. MATERIAL AND METHODSA descriptive cross-sectional study was carried out at the department of anatomy in Universal College of Medical Sciences, Bhairahawa, Nepal from September 2021 to November 2022 after ethical clearance from the same institution (IRC UCMS, Ref: UCMS/IRC/079/21). Full and segmental length of upper limb was taken, recorded with help of flexible tape. Reference points for these measurements were bony landmarks as approved in the Integrative Measurement Protocol Morphological and Behavioral Research in Human and non-human primates version 1.0 were used. Convenient sampling method was used Data was analyzed using Microsoft Excel 2016. Point estimate at 95% Confidence Interval was calculated along with frequency and percentage. RESULTSOut of two hundred fifty seven participants 141 were male and 116 were female. Total upper limb length of male is 74.17± 4.79 cm and female is 71.92 ± 4.81cm. Total upper limb length discrepancy maximum was observed 3 cm. In our study it was observed that wrist has maximum discrepancy between right and left limb followed by arm and fore arm. CONCLUSIONThe present study shows the prevalence of upper limb length discrepancy in asymptomatic Nepalese population.

Evaluating the oral delivery of GalNAc-conjugated siRNAs in rodents and non-human primates.

Oral delivery is the most widely used and convenient route of administration of medicine. However, oral administration of hydrophilic macromolecules is commonly limited by low intestinal permeability and pre-systemic degradation in the gastrointestinal (GI) tract. Overcoming some of these challenges allowed emergence of oral dosage forms of peptide-based drugs in clinical settings. Antisense oligonucleotides (ASOs) have also been investigated for oral administration but despite the recent progress, the bioavailability remains low. Given the advancement with highly potent and durable trivalent N-acetylgalactosamine (GalNAc)-conjugated small interfering RNAs (siRNAs) via subcutaneous (s.c.) injection, we explored their activities after oral administration. We report robust RNA interference (RNAi) activity of orally administrated GalNAc-siRNAs co-formulated with permeation enhancers (PEs) in rodents and non-human primates (NHPs). The relative bioavailability calculated from NHP liver exposure was <2.0% despite minimal enzymatic degradation in the GI. To investigate the impact of oligonucleotide size on oral delivery, highly specific GalNAc-conjugated single-stranded oligonucleotides known as REVERSIRs with different lengths were employed and their activities for reversal of RNAi effect were monitored. Our data suggests that intestinal permeability is highlyinfluenced by the size of oligonucleotides. Further improvements in the potency of siRNA and PE could make oral delivery of GalNAc-siRNAs as a practical solution.

Necrophilic behaviour in wild stump-tailed macaques (Macaca arctoides)

Necrophilic behavior (attempted copulation with corpses) has been scarcely reported in non-human primates, especially in the wild. Here is the first case of necrophilic behavior observed in wild stump-tailed macaques in Thailand. Six groups of total N > 460 individuals have been identified and habituated. The corpse of an adult female was found and directly observed for 2 days and by camera trap for 3 days. The cause of death could not be identified, but no prominent physical injury was detected. Within 3 days of the observation, three different males attempted copulation with the corpse. Noteworthy for this observation was that not only males in the group of the dead female but also males from different groups interacted with the corpse. Taken together, these observations suggest that some cues emanating from the corpse coupled with a nonresistant/passive orientation may have triggered these responses in the males. Given that necrophiliac responses have been scarcely reported in non-human primates, our findings provide new insight into these behaviors and to comparative thanatology in general.

Fundus Tessellation and Parapapillary Atrophy, as Ocular Characteristics of Spontaneously High Myopia in Macaques: The Non-Human Primates Eye Study.

This study aimed to evaluate the ocular characteristics associated with spontaneously high myopia in adult nonhuman primates (NHPs). A total of 537 eyes of 277 macaques with an average age of 18.53 ± 3.01 years (range = 5-26 years), raised in a controlled environment, were included. We measured ocular parameters, including spherical equivalent (SE), axial length (AXL), and intraocular pressure. The 45-degree fundus images centered on the macula and the disc assessed the fundus tessellation and parapapillary atrophy (PPA). Additionally, optical coherence tomography (OCT) was used to measure the thickness of the retinal nerve fiber layer (RNFL). The mean SE was -1.58 ± 3.71 diopters (D). The mean AXL was 18.76 ± 0.86 mm. The prevalence rate of high myopia was 17.7%. As myopia aggravated, the AXL increased (r = -0.498, P < 0.001). Compared with non-high myopia, highly myopic eyes had a greater AXL (P < 0.001), less RNFL thickness (P = 0.004), a higher incidence of PPA (P < 0.001), and elevated grades of fundus tessellation (P < 0.001). The binary logistic regression was performed, which showed PPA (odds ratio [OR] = 4.924, 95% confidence interval [CI] = 2.375-10.207, P < 0.001) and higher grades of fundus tessellation (OR = 1.865, 95% CI = 1.474-2.361, P < 0.001) were independent risk characteristics for high myopia. In NHPs, a higher grade of fundus tessellation and PPA were significant biomarkers of high myopia. The study demonstrates adult NHPs raised in conditioned rooms have a similar prevalence and highly consistent fundus changes with human beings, which strengthens the foundation for utilizing macaques as an animal model in high myopic studies.

Targeted nanoparticles for imaging and therapy of endometriosis.

In this brief review, we discuss our efforts to validate nanoplatforms for imaging and treatment of endometriosis. We specifically highlight our use of nonhuman primates and primate tissues in this effort. Endometriosis is a painful disorder of women and nonhuman primates (NHPs) where endometrium-like tissue exists outside of the uterus. There are no reliable, specific, and noninvasive diagnostic tests for endometriosis. Laparoscopic imaging remains the gold standard for identifying small endometriotic lesions in both women and monkeys. Visualizing and surgically removing microscopic lesions remains a clinical challenge. To address this challenge, we have created nanoparticle reagents that, when administered intravenously, enter endometriotic lesions both passively and by targeting endometriotic cells. The particles can carry payloads, including near-infrared fluorescent dyes and magnetic nanoparticles. These agents can be used for imaging and thermal ablation of diseased tissues. We evaluated this approach on macaque endometriotic cells, human and macaque endometrium engrafted into immunodeficient mice, in endometrium subcutaneously autografted in macaques, and in rhesus monkeys with spontaneous endometriosis. Employing these models, we report that nanoplatform-based reagents can improve imaging and provide thermal ablation of endometriotic tissues.

Preformed Vesicle Approach to LNP Manufacturing Enhances Retinal mRNA Delivery.

Complete encapsulation of nucleic acids by lipid-based nanoparticles (LNPs) is often thought to be one of the main prerequisites for successful nucleic acid delivery, as the lipid environment protects mRNA from degradation by external nucleases and assists in initiating delivery processes. However, delivery of mRNA via a preformed vesicle approach (PFV-LNPs) defies this precondition. Unlike traditional LNPs, PFV-LNPs are formed via a solvent-free mixing process, leading to a superficial mRNA localization. While demonstrating low encapsulation efficiency in the RiboGreen assay, PFV-LNPs improved delivery of mRNA to the retina by up to 50% compared to the LNP analogs across several benchmark formulations, suggesting the utility of this approach regardless of the lipid composition. Successful mRNA and gene editors' delivery is observed in the retinal pigment epithelium and photoreceptors and validated in mice, non-human primates, and human retinal organoids. Deploying PFV-LNPs in gene editing experiments result in a similar extent of gene editing compared to analogous LNP (up to 3% on genomic level) in the Ai9 reporter mouse model; but, remarkably, retinal tolerability is significantly improved for PFV-LNP treatment. The study findings indicate that the LNP formulation process can greatly influence mRNA transfection and gene editing outcomes, improving LNP treatment safety without sacrificing efficacy.

Correcting the record: Phonetic potential of primate vocal tracts and the legacy of Philip Lieberman (1934-2022).

The phonetic potential of nonhuman primate vocal tracts has been the subject of considerable contention in recent literature. Here, the work of Philip Lieberman (1934-2022) is considered at length, and two research papers-both purported challenges to Lieberman's theoretical work-and a review of Lieberman's scientific legacy are critically examined. I argue that various aspects of Lieberman's research have been consistently misinterpreted in the literature. A paper by Fitch et al.overestimates the would-be "speech-ready"capacities of a rhesus macaque, and the data presented nonetheless supports Lieberman's principal position-that nonhuman primates cannot articulate the full extent of human speech sounds. The suggestion that no vocal anatomical evolution was necessary for the evolution of human speech (as spoken by all normally developing humans) is not supported by phonetic or anatomical data. The second challenge, by Boë et al., attributes vowel-like qualities of baboon calls to articulatory capacities based on audio data; I argue that such "protovocalic"properties likely result from disparate articulatory maneuvers compared to human speakers. A review of Lieberman's scientific legacy by Boë et al.ascribes a view of speech evolution (which the authors term "laryngeal descent theory") to Lieberman, which contradicts his writings. The present article documents a pattern of incorrect interpretations of Lieberman's theoretical work in recent literature. Finally, the apparent trend of vowel-like formant dispersions in great ape vocalization literature is discussed with regard to Lieberman's theoretical work. The review concludes that the "Lieberman account"of primate vocal tract phonetic capacities remains supported by research: the ready articulation of fully human speech reflects species-unique anatomy.

Molecular Detection and Characterization of Hemotropic Mycoplasma in Assamese Macaques (Macaca assamensis) of Northern Thailand.

Hemotropic mycoplasmas, also known as hemoplasmas, are parasitic bacteria that infect red blood cells, potentially leading to varying degrees of anemia across numerous mammalian species, including nonhuman primates. The present study aims to investigate the prevalence of hemoplasma infection and identify the species involved among free-ranging Assamese macaques (Macaca assamensis) inhabiting northern Thailand. A total of 133 blood samples were collected from Assamese macaques in Chiang Rai province, Thailand, and subjected to screening for hemoplasma infection utilizing nested PCR amplification targeting the 16S rRNA gene. Positive samples were subsequently analyzed through nucleotide sequencing and phylogenetic analysis for putative species identification. Current study results revealed that 17.3% (23/133; 95% CI 11.29-24.81) of Assamese macaques tested positive for hemoplasma infection using the nested PCR assay. Partial 16S rRNA sequences derived from hemoplasma isolates in Assamese macaques exhibited 99% homology, forming a cluster within the same phylogenetic clade as "Candidatus Mycoplasma haematomacacae," previously identified in long-tailed macaques, rhesus macaques, and Japanese macaques. These findings suggest the presence of "Ca. M. haematomacacae" not only in long-tailed macaques and rhesus macaques but also in Assamese macaques in Thailand. To our knowledge, this marks the first molecular detection of "Ca. M. haematomacacae" in Assamese macaques in Thailand. These results hold significance as they enhance our understanding of hemoplasma infection distribution among macaque populations in Thailand.

Terrestriality across the primate order: A review and analysis of ground use in primates.

Terrestriality is relatively rare in the predominantly arboreal primate order. How frequently, and when, terrestriality appears in primate evolution, and the factors that influence this behavior, are not well understood. To investigate this, we compiled data describing terrestriality in 515 extant nonhuman primate taxa. We describe the geographic and phylogenetic distribution of terrestriality, including an ancestral state reconstruction estimating the frequency and timing of evolutionary transitions to terrestriality. We review hypotheses concerning the evolution of primate terrestriality and test these using data we collected pertaining to characteristics including body mass and diet, and ecological factors including forest structure, food availability, weather, and predation pressure. Using Bayesian analyses, we find body mass and normalized difference vegetation index are the most reliable predictors of terrestriality. When considering subsets of taxa, we find ecological factors such as forest height and rainfall, and not body mass, are the most reliable predictors of terrestriality for platyrrhines and lemurs.

An unusual configuration of two anomalies in the extensor digitorum profundus complex in a human.

The extensor digitorum profundus complex underwent degeneration of the ulnar segments during primate adaptation and evolution. This process resulted in the preservation of only the extensor pollicis longus and extensor indicis in some apes, including humans. Consequently, anatomical variations within the digitorum profundus complex in modern humans have been well-documented, with detailed reports on their frequency and patterns in previous studies. Here, we report an unusual arrangement involving two anomalies in the extensor digitorum profundus complex, identified in a 66-year-old Japanese male cadaver. In this cadaver, two accessory muscles differentiated from both the extensor pollicis longus and extensor indicis. Notably, the latter muscle featured a tendon bifurcating towards both the thumb and index fingers, referred to as the extensor pollicis et indicis communis. Under the extensor retinaculum, the tendon of the accessory extensor pollicis longus passed through an independent compartment, whereas that of the extensor pollicis et indicis communis traversed a compartment shared by the extensor indicis and the extensor digitorum communis. Both muscles were innervated by the posterior interosseous nerve. Previous studies have reported that the accessory slip of the extensor pollicis longus and extensor pollicis et indicis communis appear at frequencies of 0.6% and 0.4-1.4%, respectively. However, to the best of our knowledge, a configuration in which both appear simultaneously has not been reported. The data from this case could provide essential insights into the variations in the extensor digitorum profundus complex in humans and non-human primates.