The Mouse Lemur, a Genetic Model Organism for Primate Biology, Behavior, and Health

Abstract

Systematic genetic studies of a handful of diverse organisms over the past 50 years have transformed our understanding of biology. However, many aspects of primate biology, behavior, and disease are absent or poorly modeled in any of the current genetic model organisms including mice. We surveyed the animal kingdom to find other animals with advantages similar to mice that might better exemplify primate biology, and identified mouse lemurs (Microcebus spp.) as the outstanding candidate. Mouse lemurs are prosimian primates, roughly half the genetic distance between mice and humans. They are the smallest, fastest developing, and among the most prolific and abundant primates in the world, distributed throughout the island of Madagascar, many in separate breeding populations due to habitat destruction. Their physiology, behavior, and phylogeny have been studied for decades in laboratory colonies in Europe and in field studies in Malagasy rainforests, and a high quality reference genome sequence has recently been completed. To initiate a classical genetic approach, we developed a deep phenotyping protocol and have screened hundreds of laboratory and wild mouse lemurs for interesting phenotypes and begun mapping the underlying mutations, in collaboration with leading mouse lemur biologists. We also seek to establish a mouse lemur gene “knockout” library by sequencing the genomes of thousands of mouse lemurs to identify null alleles in most genes from the large pool of natural genetic variants. As part of this effort, we have begun a citizen science project in which students across Madagascar explore the remarkable biology around their schools, including longitudinal studies of the local mouse lemurs. We hope this work spawns a new model organism and cultivates a deep genetic understanding of primate biology and health. We also hope it establishes a new and ethical method of genetics that bridges biological, behavioral, medical, and conservation disciplines, while providing an example of how hands-on science education can help transform developing countries.

Rhesus macaques as a tractable physiological model of human ageing

“…Their small sizes (60 g, M. murinus ; 320 g, C. jacchus ), short lifespans (5-10 years, M. murinus ; 5-7 years, C. jacchus ), short generation times (8-10 months, M. murinus ; 20 months, C. jacchus ), and docile temperaments make both species practical and inexpensive to maintain in laboratories, particularly compared to larger-bodied monkeys and apes. The mouse lemur is attracting interest as a biomedical model due to its smaller size, greater fecundity, and faster life history, as well as the presence of parallel age-associated diseases including neurodegenerative pathologies [15]. The marmoset is far more established in laboratory settings, shares a greater phylogenetic relatedness to humans, and exhibits similar age-related diseases including diabetes, cardiovascular disease, and cancer [16].…”

Variation in reproduction of the smallest‐bodied primate radiation, the mouse lemurs (Microcebus spp.): A synopsis

“…The Malagasy mouse lemurs, with currently 24 described species, represent a species‐rich primate radiation with the smallest‐bodied primates in the world, ranging in body mass between 30 and 80 g (Hotaling et al, ; Mittermeier et al, ; Radespiel et al, ; Rasoloarison, Weisrock, Yoder, Rakotondravony, & Kappeler, ). Mouse lemurs are suggested to represent genetic model organisms for primate biology, behavior, and health (Ezran et al, ). They are nocturnal, arboreal, solitary foragers with an omnivorous diet (Lahann, ; Radespiel, ; Thorén et al, ; Zimmermann, Cepok, Rakotoarison, Zietemann, & Radespiel, ).…”

The Ontogeny of Masticatory Muscle Architecture in Microcebus murinus

“…The gray mouse lemur, M. murinus , is a small nocturnal primate native to Western Madagascar (Mittermeier et al, ). Due to its small size and manageability—especially for a primate—it exists as a model organism in numerous colonies across Europe and the United States (Martin, ; Rassoul et al, ; Ezran et al, ) in larger numbers than most other primate species. The life span for these animals in the field has been reported to be between 3 and 4 years (Bons et al, ); however, in captive environments, they tend to live to be around 5 years of age with a maximal life span of up to 11 years (Perret, ; Castanet et al, ).…”