IDENTIFICATION OF THE MEG1 GRB10 IMPRINTED GENE ON MOUSE PROXIMAL CHROMOSOME-11, A CANDIDATE FOR THE SILVER-RUSSELL-SYNDROME GENE/

In a systematic screen for maternally expressed imprinted genes using subtraction hybridization with androgenetic and normal fertilized mous e embryos, seven candidate maternally expressed genes (Megs) have been isolated, including the H19 and p57(Kip2) genes that are known to be maternally expressed, Herein, we demonstrate that an imprinted gene, M eg1, is apparently identical to Grb10 (growth factor receptor-bound pr otein 10), which is located on mouse proximal chromosome 11, Grb10 pro tein was reported to bind to the insulin receptor and/or the insulin-l ike growth factor (IGF) I receptor via its src homology 2 domain and t o inhibit the associated tyrosine kinase activity that is involved in the growth promoting activities of insulin and IGFs (IGF-I and -II), T hus, it is probable that Meg1/Grb10 is responsible for the imprinted e ffects of prenatal growth retardation or growth promotion caused by ma ternal or paternal duplication of proximal chromosome 11 with reciproc al deficiencies (MatDp.prox11 or PatDp.prox11), respectively. In the h uman, it has been reported that the maternal uniparental disomy 7 is r esponsible for the Silver-Russell syndrome (SRS) whose effects include pre-and postnatal growth retardation and other dysmorphologies, The h uman homologue GRB10 on chromosome 7q11.2-12 is a candidate gene for S ilver-Russell syndrome.