7 MOUSE PHENOTYPE RESOURCES

If you are interested in mouse phenotypes, you’ll have noticed that there are a wealth of resources available. Here’s our round-up of some of the best databases out there. Did we miss your favourite? Let us know by contacting us on Twitter @dmdduk.


Mouse Genome Informatics

 

 

 

 

 

 

Almost everyone will be familiar with this one, but no list of mouse resources would be complete without the MGI database. It covers gene characterisation, nomenclature, phenotypes, gene expression and tumour biology amongst many other datasets.

Use this resource: for a broad picture of mouse genetics. www.informatics.jax.org


Facebase

 

 

 

 

Around half of all birth defects involve the face, but in many cases the reason they occur remains unknown. The Facebase resource aims to tackle this problem with their database of head, skull and craniofacial data. The first five-year phase concentrated on the middle of the human face and the genetics of disorders such as cleft lip and palate. The second phase (which is currently underway) will expand Facebase to include other regions of the face, as well as developing new online search and analysis tools for the data.

Use this resource: if you’re specifically interested in craniofacial phenotypes. www.facebase.org


Monarch

 

 

 

 

The Monarch resource allows cross-species comparison of phenotype data without the user having detailed knowledge of each species’ genetics, development, anatomy, or the terminology used to describe it. The database contains phenotype data for many species including human, mouse, zebrafish and flies, which has been gathered from other dedicated phenotyping projects. The tools developed by Monarch allow users to explore phenotypic similarity between species and are intended to facilitate the identification of animal models of human disease.

Use this resource: to compare mouse phenotype data with phenotypes from many other species. www.monarchinitiative.org


Deciphering the Mechanisms of Developmental Disorders

DMDD LOGO

 

The DMDD database contains high-resolution images and detailed whole-embryo phenotype data for embryonic lethal knockout mouse lines. The High Resolution Episcopic Microscopy technique used for imaging allows phenotypes to be identified down to the level of abnormal positioning or morphology of individual nerves and blood vessels. Parallel screens identify placental phenotypes and carry out whole-embryo gene expression profiling, with all data freely available online. Around 80 lines have been phenotyped to date, with new data added regularly.

Use this resource: for whole-embryo images and phenotype datasets – primary screen data at an unprecedented level of detail. dmdd.org.uk


International Mouse Phenotyping Consortium

 

 

 

 

The IMPC has the ambitious goal of phenotyping knockout mice for 20,000 known and predicted mouse genes. For adult mice, the project provides primary screen data for all the major organ systems, and for many embryonic lethal lines there is also embryo data available. With nearly 6000 lines already analysed, there’s an enormous amount of data to explore.

Use this resource: to access phenotype data for a huge number of knockout mouse lines. www.mousephenotype.org


Origins of Bone and Cartilage Disease

 

 

 

OBCD is a collaboration working to identify the genetic causes of bone and cartilage disease – an important goal when you consider that around half of adults are affected by a bone or cartilage disorder. OBCD aims to phenotype mice from 1750 different knockout lines, and they have made a heatmap of their data freely available online. With nearly 500 lines phenotyped so far, there’s already a huge amount of data and much more to come.

Use this resource: if you’re specifically interested in phenotypes related to the bones and joints. www.boneandcartilage.com


eMouseAtlas

 

 

 

 

Last but not least, if you’re interested in mouse phenotypes you will probably also need information about normal mouse development. The eMouseAtlas resource provides 3D computer models of the developing mouse, covering everything from gross anatomy to detailed structure. It’s a useful point of comparison for phenotypes that have been observed in mutant mouse strains. As a nice project they have also re-digitised the original histological sections from Kaufman’s definitive book ‘The Atlas of Mouse Development‘, making the images available online in high resolution for the first time, together with their original annotations.

Use this resource: for a detailed description of normal mouse embryo morphology at any stage of development. www.emouseatlas.org

 

Tweet us if we missed your favourite database @dmdduk.

Cover image by Rama (Own work) [CC BY-SA 2.0 fr], via Wikimedia Commons.

3 NEW RESULTS FROM KNOCKOUT MOUSE SCREENS

Around a third of mammalian genes are essential for life, and the recent Nature paper from the IMPC  ‘High-throughput discovery of novel developmental phenotypes‘ [1] describes some achievements from sytematic study of these genes in knockout mice.

Screens like those of the IMPC and DMDD are vital to understand gene function on a genome-wide scale and, based on the results recently published in Nature, here are some reasons why.


FURTHER EVIDENCE THAT MOUSE DATA IS RELEVANT TO CLINICAL STUDIES

Lethal genes in the mouse are known to be enriched for human disease genes [2,3]. When additional data from the IMPC was included on the genes essential for survival of the embryo, this enrichment was increased even further. More than half of the human disease genes considered were essential for mouse embryo survival. The study also found a remarkable correlation between the core essential genes in humans and mice.

Systematic knockout mouse screens provide data that could not be derived from human patients. These new results further underline the importance of mouse models in the study of human disease, and their relevance in a clinical setting.


INCOMPLETE PHENOTYPE PENETRANCE

A suprising observation from knockout mouse screens is the incomplete penetrance of phenotypes for many lines.

One example of this is the sub-viability of lines. The IMPC has found that in around 11% of knockout lines some homozygous pups were observed, but fewer than the 1 in 4 pups predicted by Mendelian genetics. Some pups were able to survive with the homozygous gene knockout, but some weren’t.

Incomplete penetrance is a result also echoed in DMDD data. For example, in the seven Adamts3 knockout embryos studied, all display subcutaneous edema and absent lymph sac, while only two display a bifid ureter.

Click to view larger image.
Subcutaneous edema and bifid ureter (left side) observed in an Adamts3 mutant embryo. The red arrows highlight a single ureter on the right side, but two branches on the left side.

Data from systematic screens of knockout mice is showing, on an unprecedented scale, that even for a complete gene knockout, the observed phenotypes can vary from embryo to embryo. Given the standardised background and allele construction, this is a suprising result and could suggest an underlying stochastic process.


CANDIDATES GENES FOR UNDIAGNOSED HUMAN DISEASE

As part of its systematic screen, the IMPC has identified 22 essential mouse genes with human orthologs that are not known to be associated with any human disease. These are potential candidates for undiagnosed diseases and could shine new light on the causes of genetic disorders.

Efforts are continuing to study knockouts of every gene in the mouse genome. As these datasets grow in size, so too does the potential for them to help us understand gene expression and the genetic basis of human disease.

The DMDD database of embryonic-lethal mouse knockouts can be found at dmdd.org.uk.

The IMPC database of knockout mice can be found at www.mousephenotype.org.


REFERENCES

[1] The IMPC Collaboration (2016)
High-throughput discovery of novel developmental phenotypes
Nature  doi:10.1038/nature19356

[2] B. Georgi1, B. F. Voight1, M. Bućan1 (2013)
From mouse to human: evolutionary genomics analysis of human orthologs of essential genes
PLoS Genet 9(5): e1003484. doi: 10.1371/journal.pgen.1003484

1 Department of Genetics, Perelman School of Medicine, University of Pennsylvania, USA

[3] J. E. Dickerson 1, A. Zhu1, D. L. Robertson1 K. E. Hentges1 (2011)
Defining the role of essential genes in human disease
PLoS ONE, 6(11), e27368. http://doi.org/10.1371/journal.pone.0027368

1 Faculty of Life Sciences, University of Manchester, UK