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CRB Anim

Development of animal models for genetic diseases

Development of animal models for genetic diseases
Spontaneous models and diagnostic tests and Engineered models
  • Spontaneous models and diagnostic tests for genetic defects

Targeted industrial partners are the biotech companies providing genotyping services and /or biological models for medical applications (animal health and models for human health).
The development strategy of ANTAGENE estimates that the world market for diagnostic tests on genetic abnormalities in dogs will reach 50 millions euros in the coming 10 years. The market of diagnosis test in livestock is also expected to develop with the progress of genomics. Testing may become mandatory to check that a sire is free of a genetic defect before it can be used commercially. Diagnostic tests for several genetic abnormalities have already been patented:

- in dogs:

international patent 03116-01 for ichthyosis in the Golden retriever owned by CNRS (André et al., 2009) a European Patent n°08305372. 8 “Method for diagnosing and predicting cerebellar ataxia” owned by Alfort Nat. Vet School: Abitbol et al., 2008); International licences have been delivered to ANTAGENE for the marketing of the corresponding genetic tests for diagnostic and prediction; the income was 10 k€ in 2010.
 in pigs :patent PCT/EP2000/009896 on AMPK gene for meat quality and RN mutation, is owned at 40% by INRA and shared with two institutions from Sweden and Germany, income from the patent represents a total of 600 k€ for INRA since 2000.

- in cattle :

CVM is a genetic defect of the skeleton patented by a Danish institution, to which LABOGENA is returning 26 k€ each year for 2200 tests.

- in horses:

Equinom (Ireland) is marketing the ‘speed gene’ test, with a SNP in the myostatin gene associated with higher racing performance, at a price negociated between 500 and 1000 € according to number of samples.

The aim of CRB-Anim is to facilitate the molecular identification of genetic defects by research teams who will in turn decide about a patenting strategy. It is expected that several new mutations will be identified thanks to the genomic collections of CRB-Anim.
As observed with the Cani-DNA bioBank, a major economic return of the biobank is the use of samples to discover novel genes, novel protein and biological pathways in the field of veterinary research and breeding but also in the field of human medical research. For example, Oncovet Clinical Research is a French Contract Research Organisation interested in the dog models of the Cani-Dna biobank. The same situation can be encountered with livestock species and partners will share their know-how in the field of economic exploitation of results obtained from collections. For instance, the ANR Swan project is co-funded by pig breeders and is expected to identify causal mutations for congenital abnormalities.
Moreover, such tests can also be applied on frozen semen in order to characterize the stored semen before use. Those tests are particularly valuable for the breeding strategy. They can be used to avoid the birth of affected progeny by adapting crosses and taking care not to deplete the gene pool. Genetic tests will be proposed to breeding organisations, individual breeders and veterinarians.
Technical adjustments, new methods and novel development to perform genetic tests are also part of the outcomes. These developments will involve more particularly the private partners of CRB-Anim, ANTAGENE and LABOGENA which are willing to exploit the results by claiming licenses.

  • Engineered models

Animal models are being developed by research teams in other species than rodents. CRB-Anim will offer the possibility to store gametes, embryos or cells from such models for further by public or private laboratories. For instance, in fishes, a unique model has been developed in the rainbow trout to study sexual differentiation (Baron et al., 2007,2008) and rare homozygous clones are being produced (at INRA GABI) to study the relationship between genetics and environment such as nutrition (diet replacement with vegetal proteins) and temperature in a context of global warming (Quillet et al, 2007; Grima et al, 2008).

The ability to perform precise genetic engineering such as gene targeting for invalidation or surexpression, and allelic replacement in non rodent mammals would greatly benefit biomedical research by enabling, for example, the development of genetically defined rabbit models of human diseases. More than 10 years after the first demonstration, there are a few examples of gene targeting in mammals other than mice: COL1A1 in sheep [(McCreath et al., 2000], PRNP in sheep, cattle, and goats [Denning et al., 2001, Kuroiwa et al., 2004, Yu et al., 2006), GGTA1 in pigs (Dai et al., 2002, Lai et al., 2002), IGH in cattle (Kuroiwa et al., 2004) LIPH in rabbit (Diribarne et al., 2011), and CFTR in pigs (Rogers et al., 2008). Technological developments proposed by CRB-Anim on iPS and nuclear transfer are expected to facilitate the development of such models. INRA partner is currently working on a transgenic rabbit for the 8508 mutation of the CFTR gene in order to propose a model for testing new therapies against mucoviscidosis.