Analysis of imprinted murine Peg3 locus in transgenic mice.
Peg3 is an imprinted gene exclusively expressed from the paternal allele. It encodes a C(2)H(2) type zinc-finger protein and is involved in maternal behavior. It is important for TNF-NFkB signaling and p53-mediated apoptosis. To investigate the imprinting mechanism and gene expression of Peg3 and its neighboring gene(s), we used a 120 kb Peg3-containing BAC clone to generate transgenic mice. The BAC clone contains 20 kb of 5' and 80 kb of 3' flanking DNA, and we obtained three transgenic lines. In one of the lines harboring one copy of the transgene, Peg3 was imprinted properly. In the other two lines, Peg3 was expressed upon both maternal and paternal transmission. Imprinted expression was linked to the differential methylation of a region (DMR) upstream of the Peg3 gene. A second, maternally expressed gene, Zim1, present on the transgene was expressed irrespective of parental inheritance in all lines. These data suggest that, similar to other imprinted genes within domains, Peg3 and Zim1 are regulated by one or more elements lying at a distance from the genes. The imprinting of Peg3 seen in one line may reflect the presence of a responder sequence. Concerning the expression of the Peg3 transgene, we detected appropriate expression in the adult brain. However, this was not sufficient to rescue the maternal behavior phenotype seen in Peg3 deficient animals.
Szeto
Irene Y Y
IY
Wellcome Trust/Cancer Research UK Institute of Cancer and Developmental Biology and Department of Physiology, University of Cambridge, Tennis Court Road, Cambridge, CB2, 1QR, UK.
Barton
Sheila C
SC
Keverne
E B
EB
Surani
Azim M
AM
D000818:Animals; D002352:Carrier Proteins; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018392:Genomic Imprinting / Q000235:genetics*; D051741:Kruppel-Like Transcription Factors; D008297:Male; D008425:Maternal Behavior; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000662:veterinary; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; C097901:Peg3 protein, mouse; D014157:Transcription Factors; C119426:Zim1 protein, mouse; D004247:DNA; D011494:Protein Kinases