Olfactory functions assessment of the mouse model of the human 22q11.2 deletion syndrome

Abstract

Schizophrenia is a neuropsychiatric disease with 1% prevalence in the population. Patients affected by this disorder suffer from negative symptoms such as alogia or avolition; and from positive symptoms such as hallucinations or delusions. Cognitive disabilities such as working memory and language function deficits have often been indexed in Schizophrenia’s symptomatology. Even though its symptoms are well known, the etiology of Schizophrenia remains unclear. However, the discovery of the Velo-Cardio-Facial syndrome (VCFS) put one step further in understanding the mechanism of the disease. Indeed, a deletion on the chromosome 22 in the q11.2 band causes this syndrome and one of its most common symptoms is Schizophrenia. Since then, a quasi-perfect synteny between one part of the 22q11.2 region in humans and the chromosome 16qA3 has been discovered and several mouse model of the VCFS form of Schizophrenia have been engineered. In my thesis, the olfactory performances of LgDel+/- mice, one of several murine model of the human 22q11.2 deletion, have been studied. Indeed, idiopathic schizophrenics as well as VCFS patients show olfactory deficits such as olfactory hallucinations or olfactory identification and discrimination impairments. During my project, we could find that odorant detection is intact in mutant mice using functional imaging. Behavioral experimentations with an olfactometer allow testing primary olfactory discrimination as well as detection threshold and rule flexibility. None of them are impaired in LgDel+/- mice however; using also the olfactometer, there are strong presumptions suggesting that attention and olfactory memory seem to be defective in LgDel+/- mice