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A comprehensive and comparative phenotypic analysis of the collaborative founder strains identifies new and known phenotypes.

ABSTRACT: The collaborative cross (CC) is a large panel of mouse-inbred lines derived from eight founder strains (NOD/ShiLtJ, NZO/HILtJ, A/J, C57BL/6J, 129S1/SvImJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ). Here, we performed a comprehensive and comparative phenotyping screening to identify phenotypic differences and similarities between the eight founder strains. In total, more than 300 parameters including allergy, behavior, cardiovascular, clinical blood chemistry, dysmorphology, bone and cartilage, energy metabolism, eye and vision, immunology, lung function, neurology, nociception, and pathology were analyzed; in most traits from sixteen females and sixteen males. We identified over 270 parameters that were significantly different between strains. This study highlights the value of the founder and CC strains for phenotype-genotype associations of many genetic traits that are highly relevant to human diseases. All data described here are publicly available from the mouse phenome database for analyses and downloads.

SUBMITTER: Kollmus H

PROVIDER: S-EPMC7060152 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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A comprehensive and comparative phenotypic analysis of the collaborative founder strains identifies new and known phenotypes.

Kollmus Heike H Fuchs Helmut H Lengger Christoph C Haselimashhadi Hamed H Bogue Molly A MA Östereicher Manuela A MA Horsch Marion M Adler Thure T Aguilar-Pimentel Juan Antonio JA Amarie Oana Veronica OV Becker Lore L Beckers Johannes J Calzada-Wack Julia J Garrett Lillian L Hans Wolfgang W Hölter Sabine M SM Klein-Rodewald Tanja T Maier Holger H Mayer-Kuckuk Philipp P Miller Gregor G Moreth Kristin K Neff Frauke F Rathkolb Birgit B Rácz Ildikó I Rozman Jan J Spielmann Nadine N Treise Irina I Busch Dirk D Graw Jochen J Klopstock Thomas T Wolf Eckhard E Wurst Wolfgang W Yildirim Ali Önder AÖ Mason Jeremy J Torres Arturo A Balling Rudi R Mehaan Terry T Gailus-Durner Valerie V Schughart Klaus K Hrabě de Angelis Martin M

Mammalian genome : official journal of the International Mammalian Genome Society 20200214 1-2

The collaborative cross (CC) is a large panel of mouse-inbred lines derived from eight founder strains (NOD/ShiLtJ, NZO/HILtJ, A/J, C57BL/6J, 129S1/SvImJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ). Here, we performed a comprehensive and comparative phenotyping screening to identify phenotypic differences and similarities between the eight founder strains. In total, more than 300 parameters including allergy, behavior, cardiovascular, clinical blood chemistry, dysmorphology, bone and cartilage, energy meta ...[more]

PMID: 32060626

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Project description:The collaborative cross (CC) founder strains include five classical inbred laboratory strains (129S1/SvlmJ, A/J, C57BL/6J (B6), NOD/ShiLtJ, and NZO/HILtJ) and three wild-derived strains (CAST/EiJ, PWK/PhJ (PWK) and WSB/EiJ) The strains encompass 89% of the genetic diversity available in Mus musculus and about 10 to 20 times more genetic diversity than found in Homo sapiens. For more than 60 years the B6 strain has been used as the model strain for high ethanol preference/high consumption. However, another one of the CC founder strains, PWK, was identified as a high ethanol preference/high consumption strain. The current study determined how the transcriptomes of the B6 and PWK strains differed from the 6 low preference CC strains across 3 nodes of the brain addiction circuit. RNA-Seq data were collected from the central nucleus of the amygdala, the nucleus accumbens core and the prelimbic cortex. Differential expression (DE) analysis was performed in each of these brain regions for all 28 possible pairwise comparisons of the CC founder strains. Unique genes for each strain were identified by selecting for genes that differed significantly (false discovery rate (FDR) < 0.05) from all other strains in the same direction. B6 was identified as the most distinct inbred laboratory strain, having the highest number of total differently expressed genes (DEGs) and DEGs with high log fold change, and unique genes compared to other CC strains. Less than 50 unique DEGs were identified in common between B6 and PWK within all three brain regions, indicating the strains potentially represent two distinct genetic signatures for risk for high ethanol-preference. 238 DEGs were found to be commonly different between B6, PWK and the average expression of the remaining CC strains within all three regions. The commonly different up-expressed genes were significantly enriched (FDR < 0.001) among genes associated with neuroimmune function. These data compliment the observation that neuroimmune signaling is key to understanding alcohol use disorder and and support use of these 8 strains and the highly heterogeneous mouse populations derived from them to identify alcohol-related brain mechanisms and treatment targets.

Dataset Information

A comprehensive and comparative phenotypic analysis of the collaborative founder strains identifies new and known phenotypes.

Publications

A comprehensive and comparative phenotypic analysis of the collaborative founder strains identifies new and known phenotypes.

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