Mir-17-92, a preclinical model of feingold syndrome

Feingold Syndrome (FS) is an autosomal dominant disorder. The main clinical features are microcephaly, learning disabilities, short middle phalanges, relative short stature, oesophageal/duodenal atresia. FS is caused by germline loss-of-function mutations involving the MYCN gene at 2p24.1. However, very recently germline hemyzygous microdeletions at 13q31.3 have been identified by de Pontual et al., 2011. These authors reported that a subset of patients affected by Feingold Syndrome, carry hemizygous loss of the entire miR-17~92 cluster. To determine whether the developmental abnormalities observed in FS patients could be attributed to reduced miR-17~92 expression, mice carrying targeted deletion of the miR- 17~92 cluster 17 have been generated. Although several of the physical key features observed in FS patients carrying a hemizygous deletion for miR-17~92 are also present in miR-17~92∆/+ mice, to our knowledge no scientific description of specific learning/cognitive disabilities, mental retardation, and specific brain alterations has been reported in animal model of FS. The major aim of our study has been to identify specific learning/cognitive disabilities in the genetic murine model of FS (miR-17~92∆/+ mice, (miR17-92)). In this work we investigated the behavioral phenotype of mice miR17-92 from early post-natal development (PND4) to adulthood. Moreover, neurochemical alterations in specific brain areas (as suggested by results of behavioral tests) have been investigated. The use of such mouse model will make easier to identify early behavioral “markers” of cognitive and/or learning disabilities and to predispose adequate strategies to prevent deleterious consequences in adult life.