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 mouse 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, Meg1, is apparently identical to Grb10 (growth factor receptor-bound protein 10), which is located on mouse proximal chromosome 11. Grb10 protein was reported to bind to the insulin receptor and/or the insulin-like growth factor (IGF) I receptor via its src homology 2 domain and to inhibit the associated tyrosine kinase activity that is involved in the growth promoting activities of insulin and IGFs (IGF-I and -II). Thus, it is probable that Meg1/Grb10 is responsible for the imprinted effects of prenatal growth retardation or growth promotion caused by maternal or paternal duplication of proximal chromosome 11 with reciprocal deficiencies (MatDp.prox11 or PatDp.prox11), respectively. In the human, it has been reported that the maternal uniparental disomy 7 is responsible for the Silver-Russell syndrome (SRS) whose effects include pre- and postnatal growth retardation and other dysmorphologies. The human homologue GRB10 on chromosome 7q11.2-12 is a candidate gene for Silver-Russell syndrome.
Miyoshi
N
N
Gene Research Center, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama-226, Japan.
Kuroiwa
Y
Y
Kohda
T
T
Shitara
H
H
Yonekawa
H
H
Kawabe
T
T
Hasegawa
H
H
Barton
S C
SC
Surani
M A
MA
Kaneko-Ishino
T
T
Ishino
F
F
D000818:Animals; D002875:Chromosomes; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004392:Dwarfism / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D051383:GRB10 Adaptor Protein; D018392:Genomic Imprinting; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000502:physiology; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D009693:Nucleic Acid Hybridization; D011506:Proteins / Q000235:genetics*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D015398:Signal Transduction; D013002:Somatomedins / Q000502:physiology; D013577:Syndrome
C493964:CDKN1C protein, human; C493965:Cdkn1c protein, mouse; D050761:Cyclin-Dependent Kinase Inhibitor p57; C495959:Grb10 protein, mouse; C094335:H19 long non-coding RNA; D007328:Insulin; D009124:Muscle Proteins; D009687:Nuclear Proteins; D011506:Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D013002:Somatomedins; D051383:GRB10 Adaptor Protein; D066246:ErbB Receptors