Wild-derived mice: from genetic diversity to variation in immune responses

Abstract

Classical inbred mouse strains have historically been instrumental in mapping immunological traits. However, most of the classical strains originate from a relatively limited number of founder animals, largely within the Mus musculus domesticus subspecies. Therefore, their genetic diversity is ultimately limited. For this reason, it is not feasible to use these mice for exhaustive interrogation of immune signaling pathways. In order to investigate networks through forward genetic analysis, larger genetic diversity is required than is introduced under laboratory conditions. Recently, inbred strains from other mouse subspecies were established such as Mus musculus castaneus and Mus musculus musculus, which diverged from a shared common ancestor with Mus musculus domesticus more than one million years ago. A direct genomic comparison clearly demonstrates the evolutionary divergence that has occurred between wild-derived mice and the classical inbred strains. When compared to classical inbred strains, wild-derived mice exhibit polymorphisms every 100-200 base pairs. Studying the molecular basis of these traits provides us with insight into how the immune system can evolve regulatory features to accommodate environment-specific constraints. Because most wild-derived strains are able to breed with classical inbred mice, they represent a rich source of evolutionarily significant diversity for forward genetic studies. These organisms are an emerging, though still largely unexplored, model for the identification and study of novel immunological genes.

Characterization of the blood–brain barrier in genetically diverse laboratory mouse strains

“…S4d, e, Additional file 3 : Table S3). Wild-derived mice compared to long inbred mice showed differences in susceptibility to viral and bacterial infections, and immune response [ 31 , 32 ]. Accordingly, we detected also differences in EC expression of genes that play a role in immune response— Ly6c1 , H2-D1, B2m , Cp or Ifnar1 (Fig.…”

Burkholderia pseudomallei invades the olfactory nerve and bulb after epithelial injury in mice and causes the formation of multinucleated giant glial cells in vitro

“…These findings may also suggest that outbred mice are more resistant to olfactory nerve infection than inbred mice. Outbred mice are well known to exhibit stronger resistance to infections, to be more "immunocompetent" and to better reflect immune responses in humans than inbred mice [57][58][59][60][61][62][63][64][65]. Differences in the response to B. pseudomallei infection has also been demonstrated between different inbred mouse strains.…”

Biotechnology for Wildlife

“…As most of the classical mice strains originate from a limited number of founder stock (e.g., Mus musculus domesticus subspecies), their genetic diversity is finally limited which make them less suitable for exhaustive experimentation. Wild mice-derived strains with ability to breed with inbred mice strains are deemed to be more suitable for evolutionary and immunological studies (Poltorak et al 2018).…”