Phenotyping


Igf-1 deficient mouse,
animal model of human
sensorineural hearing loss 
The study of animal models of human diseases is a basic part of biomedical research and in particular in the area of rare diseases. In the last few years genetically modified mice have become the most widely used models and have enabled more in-depth knowledge in the study of the biological functions of genes of interest (functional genomics), as well as regarding the relationship existing between genotype and phenotype.

The analysis of the phenotype of these models is vital for finding out the functional consequences of a mutation, understanding the physiopathology of the disease, identifying new diagnostic and prognostic indicators, as well as for exploring new therapeutic approaches based on scientific hypotheses.

Phenotyping is the molecular, morphological and/or functional characterisation of a specific system (respiratory, sensorial, muscular, neural etc.), combining different techniques (molecular biology, histology, imaging techniques and in vivo functional tests) with the aim of identifying the alterations associated with a specific genetic mutation and establishing models of human diseases.

From the bioethical standpoint, the development of non-invasive techniques and standardised phenotyping procedures enables reducing the number of animals used in experimentation and complying with FELASA, directives, as well as reducing the costs of generation and maintenance.

PHENOTYPING: HOW IS THIS DONE?

The complete phenotyping of a mouse line can be split into three phases:

Phase I: all the systems are analysed in general and non-invasively with simple tests seeking phenotypes of interest. This requires a large number of animals and a sound statistical study of the data. The equipment is simple and with a moderate cost, and does not require any highly specialised training.

Phase II (under way): after identifying the altered functions, the phenotype is confirmed by a more specialised analysis on a smaller number of animals and the use of more sophisticated (invasive and non-invasive) techniques which provide detailed information. The cost of the equipment is higher and its use requires some level of specialisation and training.

Phase III: an exhaustive study on selected animals, performing invasive experiments and specifically designed tests. Both the equipment and the experience required are highly specialised.

Systematic and systemic phenotyping (including all the organs and systems for studying the pleiotropic effects of many genes) of all the lines of mutant mice requires having the appropriate technology, highly qualified personnel and developing standardised and validated protocols.

SEFALer was set up to respond to the growing need for access to secondary phenotyping found by research groups in rare diseases.