Successful long term collaborations with French and European partners (Fondation maladies rares, A.F.S.C.-C.F.C, Gencodys Consortium,…) allowed generation of customed mouse models for researchers investigating gene function and human pathophysiology.

More than 50 mouse rare disease models are now available for your research.

Find your model !

What is a rare disease ?

A disease or disorder is defined as rare in Europe when it affects less than 1 in 2,000.

Over 7,000 rare diseases are now described, meaning that 3 million people are affected in France. This number is between 27 and 36 million people in Europe, affecting between 6 and 8% of the population in his life. 

• 80% of rare diseases have identified genetic origins, mostly with a single gene involved. The genes responsible have been identified in approximately 45% of these disorders, suggesting there are 4,000 to be discovered.  For rare genetic diseases for which a gene has been identified, the function and pathophysiology are commonly poorly understood, thus limiting development of appropriate therapeutics.  
• Others are the result of infections (bacterial or viral), allergies and environmental causes, or are degenerative and proliferative.
• 50% of rare diseases affect children.
• Rare diseases are usually severe, chronic, debilitating and often life-threatening.
• For most rare diseases, there is currently no treatment, and many challenges remain.
• Currently, patients must often face the disease with, at best, treatments against the symptoms.

All the page content is based on the following ressources : Rare Disease Day's web site, the last report from the European Union Committee of Experts on Rare Diseases (EUCERD) European Report 2014.

PHENOMIN supports biomedical research on rare diseases

Since 2009, when the global research community started to apply modern genomics to rare disease research, scientists’ ability to identify the causative genes of diseases has increased exponentially. The genes of some 3,500 – 4,000 diseases are still unknown, but 5 to 10 of these new genes are found almost every week. Medical research is being transformed. Since 80% of rare disease are genetics, the mouse model became crucial in fundamental research for understanding rare diseases. 

Given the low number of people with (Less than 1 / 2,000 patient in Europe), few studies have conducted by lack of staff significant. Rare diseases (including neuromuscular, metabolic, infectious, autoimmune, and cancer susceptibility), are generally serious and disabling in 65% known cases. The vast majority are also orphaned, which is to say that there is no therapeutic treatment. Mouse models for these disorders are triply useful.  Firstly, the models are useful for decrypting the mechanisms behind of the specific disease. Secondly, a platform for testing therapies, as illustrated by recent work published by Françoise Muscatelli’s team at the Institute of Neurobiology Mediterranean (Inmed, Marseille) with respect to the Prader Willi Syndrome, one of our oldest scientific collaborations. Finally, research into rare diseases can benefit research into common sporadic disorders like obesity and cardiovascular diseases, including strokes and heart attacks. Ongoing work with families affected by rare diseases will, step-by-step, offer insights into the details of the molecular processes that underlie common diseases, and this will eventually lead to the development of new therapies that may also have wider applications.

Behind all these argues PHENOMIN keeps its involvement in fuctional genomics research in the field of rare diseases.

Our collaboration with the Fondation maladies rares

PHENOMIN shares and opens its activities/services to the French scientific community through joint calls with the Fondation maladies rares. 4 calls for projects were already launched since 2013 and have given a significant boost to the development of mouse models in the field of rare disease. 53 projects have been or are being realized from 145 submissions. All generated models are available after 2 years embargo.

Call 1, February 2013=> 20 new mouse models

Call 2, January 2015 => 13 new mouse models 

Call 3, January 2017 => 12 new mouse models

Call 4, March 2019 => 5 new mouse models and 3 rat models

• These calls help to gain a better understanding of the pathophysiological mechanisms involved in rare diseases whose defective genes have been identified. Indeed, the Conditional Knock-Out (cKO), Knock-In (KI) and transgenic (TG) genetically modified mouse models together with the wealth of associated phenotypic data, will serve as a valuable, freely available, resource for French researchers investigating gene function and human pathophysiology. 

• These calls support therapeutic proofs of concept, at the pre-clinical in vivo level. Indeed, producing these models meets a key objective in the development of a therapeutic strategy. After their initial in vitro testing, therapeutic proofs of concept must be tested in a living model that recapitulates as closely as possible both the phenotype and biological defects associated to the human disease. Such a model should provide appropriate data regarding the safety and the efficiency of the drug, thus evaluating its benefit/risk ratio, prior to conduct early phases of a therapeutic trial.

Our involvement in European research consortia

GENCODYS was a research consortium dedicated to discover the functions and dysfunctions of the brain. It works on “Genetic and Epigenetic Networks in Cognitive Dysfunction”. With this knowledge the consortium aims to work on developing possible cures and patient information. 

The consortium was funded by the European Union under the 7th framework program (Health- 241995). The consortium counted 16 members, 13 academic research groups, 2 SMEs and a patient network organization. Most consortium members are from European member states (namely Austria, Belgium, France, Germany, Great Britain and The Netherlands) but there are two non-European members (namely Iran and Pakistan).The funding was stopped in April 2016.

Finally, the consortium have supported scientific researches and generation of mouse models. 

• 2019: A new mice model representing  a relevant model for further investigations of the physiopathology of cortical malformations. The model partially mimics the human phenotype of the de novo heterozygous missense variants in the γ-tubulin gene TUBG1 which have been linked to human malformations of cortical development associated with intellectual disability and epilepsy. TUBG1 missense variants underlying cortical malformations disrupt neuronal locomotion and microtubule dynamics but not neurogenesis. Ivanova EL, Gilet JG, Sulimenko V, Duchon A, Rudolf G, Runge K, Collins SC, Asselin L, Broix L, Drouot N, Tilly P, Nusbaum P, Vincent A, Magnant W, Skory V, Birling MC, Pavlovic G, Godin JD, Yalcin B, Hérault Y, Dráber P, Chelly J, Hinckelmann MV. Nat Commun. 2019 May 13;10(1):2129. doi: 10.1038/s41467-019-10081-8.
• 2018: A new mouse models that support the high conservation of functional genomics in mammals; researchers from PHENOMIN highlighted striking similarities between the mouse phenotype and a cohort of 33 male patients with ARX c.428_451dup24. A new mouse model of ARX dup24 recapitulates the patients' behavioral and fine motor alterations. Dubos A, Meziane H, Iacono G, Curie A, Riet F, Martin C, Loaëc N, Birling MC, Selloum M, Normand E, Pavlovic G, Sorg T, Stunnenberg HG, Chelly J Humeau Y, Friocourt G, Hérault Y. Hum Mol Genet. 2018 Jun 15;27(12):2138-2153
• 2018: In collaboration with the teams of Hendrik Stunnenberg and Hans van Bokhoven from the Raboud University (Nijmegen, Netherlands),  PHENOMIN's team linked behavioural phenotypes and epigenetic analyses and disclosed part of the neurocognitive physiopathological mechanism in Kleeftstra syndrome, a rare disease with intellectual disability, autism spectrum disorders and other developmental defects caused by EHMT1 gene haploinsufficiency in humans. Increased H3K9 methylation and impaired expression of Protocadherins are associated with the cognitive dysfunctions of the Kleefstra syndrome. Giovanni Iacono, Aline Dubos, Hamid Méziane, Marco Benevento, Ehsan Habibi Amit Mandoli, Fabrice Riet, Mohammed Selloum, Robert Feil, Huiqing Zhou,Tjitske Kleefstra, Nael Nadif Kasri, Hans van Bokhoven ,Yann Herault, and Hendrik G Stunnenberg. Nucleic Acids Research, gky196, 15 March 2018.
• 2017: PHENOMIN's team has recently published the identification of a major gene involved in Koolen-de-vries syndrome, a rare disease discovered in 2008 and remains unexplained at the genetic and molecular level up to now (Mouse models of 17q21.31 microdeletion and microduplication syndromes highlight the importance of Kansl1 for cognition. Arbogast T, Iacono G, Chevalier C, Afinowi NO, Houbaert X, van Eede MC, Laliberte C, Birling MC, Linda K, Meziane H, Selloum M, Sorg T, Nadif Kasri N, Koolen DA, Stunnenberg HG, Henkelman RM, Kopanitsa M, Humeau Y, De Vries BBA, Herault Y. PLoS Genet July 13, 2017).

Our involvement in International Mouse Phenotype Consortium

The goal of the International Mouse Phenotyping Consortium (IMPC) is to discover functional insight for every gene by generating and systematically phenotyping 20,000 knockout mouse strains.

For clinical researchers who are looking for connections between gene and disease, IMPC is a gene phenotyping discovery resource that provides an unprecedent volume of high quality data. Clinicians can use IMPC data to find relevant mouse models to human disease by orthologous gene and by shared phenotypic features.

Suggested secondary analysis

Models and Challenges