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Abstract Mouse is the mammalian model of choice to study human health and disease due to its size, ease of breeding and the natural occurrence of conditions mimicking human pathology. Here we design and validate multiple reaction monitoring mass spectrometry (MRM-MS) assays for quantitation of 2118 unique proteins in 20 murine tissues and organs. We provide open access to technical aspects of these assays to enable their implementation in other laboratories, and demonstrate their suitability for proteomic profiling in mice by measuring normal protein abundances in tissues from three mouse strains: C57BL/6NCrl, NOD/SCID, and BALB/cAnNCrl. Sex- and strain-specific differences in protein abundances are identified and described, and the measured values are freely accessible via our MouseQuaPro database: http://mousequapro.proteincentre.com . Together, this large library of quantitative MRM-MS assays established in mice and the measured baseline protein abundances represent an important resource for research involving mouse models.

Abstract We proteotyped blood plasma from 30 mouse knockout strains and corresponding wild-type mice from the International Mouse Phenotyping Consortium. We used targeted proteomics with internal standards to quantify 375 proteins in 218 samples. Our results provide insights into the manifested effects of each gene knockout at the plasma proteome level. We first investigated possible contamination by erythrocytes during sample preparation and labeled, in one case, up to 11 differential proteins as erythrocyte originated. Second, we showed that differences in baseline protein abundance between female and male mice were evident in all mice, emphasizing the necessity to include both sexes in basic research, target discovery, and preclinical effect and safety studies. Next, we identified the protein signature of each gene knockout and performed functional analyses for all knockout strains. Further, to demonstrate how proteome analysis identifies the effect of gene deficiency beyond traditional phenotyping tests, we provide in-depth analysis of two strains, C8a −/− and Npc2 +/− . The proteins encoded by these genes are well-characterized providing good validation of our method in homozygous and heterozygous knockout mice. Ig alpha chain C region, a poorly characterized protein, was among the differentiating proteins in C8a −/− . In Npc2 +/− mice, where histopathology and traditional tests failed to differentiate heterozygous from wild-type mice, our data showed significant difference in various lysosomal storage disease-related proteins. Our results demonstrate how to combine absolute quantitative proteomics with mouse gene knockout strategies to systematically study the effect of protein absence. The approach used here for blood plasma is applicable to all tissue protein extracts.

To support climate change adaptation in the communities of Nunavik, an innovative multitechnique approach to map permafrost conditions and assess risks of geohazards at the community-scale level was applied. Four maps were produced for each community: (1) a surficial geology map, (2) a map of permafrost conditions based on ground-ice content and depth to bedrock, (3) a map of potential for construction, and (4) a geohazard risk assessment map. Local ground temperature data from thermistor cables were used to calibrate 1D numerical models to estimate future permafrost temperature changes and probable rates of degradation in different environmental settings within the communities and under different climate change scenarios for the 2019–2100 period. Throughout this project, abundant consultations were held in communities and with stakeholders to better understand their concerns and to provide pragmatic recommendations for improving construction methods and land-use planning to face the challenges of permafrost thaw. Specific recommendations were made to the higher levels of government for improving construction practices. Inuit aspirations, culture, and leadership remain essential in integrating permafrost geotechnical knowledge in planning a safe future for the communities.