The mouse genome

Abstract

The house mouse has been used as a privileged model organism since the early days of genetics, and the numerous experiments made with this small mammal have regularly contributed to enrich our knowledge of mammalian biology and pathology, ranging from embryonic development to metabolic disease, histocompatibility, immunology, behavior, and cancer. Over the past two decades, a number of large-scale integrated and concerted projects have been undertaken that will probably open a new era in the genetics of the species. The sequencing of the genome, which will allow researchers to make comparisons with other mammals and identify regions conserved by evolution, is probably the most important project, but many other initiatives, such as the massive production of point or chromosomal mutations associated with comprehensive and standardized phenotyping of the mutant phenotypes, will help annotation of the ∼25,000 genes packed in the mouse genome. In the same way, and as another consequence of the sequencing, the discovery of many single nucleotide polymorphisms and the development of new tools and resources, like the Collaborative Cross, will contribute to the development of modern quantitative genetics. It is clear that mouse genetics has changed dramatically over the last 10-15 years and its future looks promising.

The Problem of Passenger Genes in Transgenic Mice

“…21,22 This level of variation will be similar between other pairs of common inbred strains, such as 129, DBA, BALB/c, or AKR. 23 To illustrate the problem, we list in Table 2 the genes whose expression levels show common variations resulting from the passenger region flanking the Pon3 gene knockout shown in Figure 2. Altogether, about 40 genes exhibited variations in transcript levels, and a number of these have been found to affect atherosclerosis in transgenic studies, including paraoxonase, 2 lipoprotein lipase, and Cxcr6.…”

Caspase-4 Interacts with TNF Receptor-Associated Factor 6 and Mediates Lipopolysaccharide-Induced NF-κB-Dependent Production of IL-8 and CC Chemokine Ligand 4 (Macrophage-Inflammatory Protein-1β)

“…A particular advantage of using cells from humans compared with mice is the frequent and substantial species differences in their immune systems; for example, the absence of an exact homolog of human IL-8 in mice (41,42). Using small hairpin RNA (shRNA) knockdown technology, we generated stable human monocytic cell lines with massively reduced expression of caspase-4, and demonstrated that caspase-4 plays an important role in the classical LPS-induced TLR4-signaling pathway that leads to NF-B activation and consequent up-regulation and secretion of IL-8 and CCL4.…”

Macrophage Polarization at the Crossroad Between HIV-1 Infection and Cancer Development

“…12 Nonetheless, significant differences between mice and humans exist in the development of the immune system as well as in the activation of both the innate and adaptive immune responses. Concerning macrophage polarization, both similarities and differences have been reported between man and mouse, as summarized in the Table. In particular, one of the best surface markers used for determining the distribution and function of mouse macrophages is Ly-71 (F4/80), 13,30 which is believed to play an immunoregulatory role through the interaction with an unidentified cellular ligand expressed by other immune effectors cells.…”