|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
Development, Vol 128, Issue 10 1881-1887, Copyright © 2001 by Company of Biologists
JOURNAL ARTICLES |
A Wutz, HC Theussl, J Dausman, R Jaenisch, DP Barlow and EF Wagner
Research Institute for Molecular Pathology (IMP), Dr Bohr-Gasse 7, A-1030 Vienna, Austria. Wagner@nt.imp.
In the mouse the insulin-like growth factor receptor type 2 gene (Igf2r) is imprinted and maternally expressed. Igf2r encodes a trans-membrane receptor that transports mannose-6-phosphate tagged proteins and insulin-like growth factor 2 to lysosomes. During development the receptor reduces the amount of insulin-like growth factors and thereby decreases embryonic growth. The dosage of the gene is tightly regulated by genomic imprinting, leaving only the maternal copy of the gene active. Although the function of Igf2r in development is well established, the function of imprinting the gene remains elusive. Gene targeting experiments in mouse have demonstrated that the majority of genes are not sensitive to gene dosage, and mice heterozygous for mutations generally lack phenotypic alterations. To investigate whether reduction of Igf2r gene dosage by genomic imprinting has functional consequences for development we generated a non-imprinted allele (R2 ). We restored biallelic expression to Igf2r by deleting a critical element for repression of the paternal allele (region 2) in mouse embryonic stem cells. Maternal inheritance of the R2 allele has no phenotype; however, paternal inheritance results in bialleleic expression of Igf2r, which causes a 20% reduction in weight late in embryonic development that persists into adulthood. Paternal inheritance of the R2 allele rescues the lethality of a maternally inherited Igf2r null allele and a maternally inherited Tme (T-associated maternal effect) mutation. These data show that the biological function of imprinting Igf2r is to increase birth weight and they also establish Igf2r as the Tme gene.
This article has been cited by other articles:
|
|
 |
|
  A. Thurston, J. Taylor, J. Gardner, K. D Sinclair, and L. E Young Monoallelic expression of nine imprinted genes in the sheep embryo occurs after the blastocyst stage Reproduction, January 1, 2008; 135(1): 29 - 40. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Nikolettos, B. Asimakopoulos, and I. S. Papastefanou Intracytoplasmic Sperm Injection-An Assisted Reproduction Technique That Should Make Us Cautious About Imprinting Deregulation Reproductive Sciences, July 1, 2006; 13(5): 317 - 328. [Abstract] [PDF]
|
|
|
|
 |
|
 J. Feng, C. Bi, B. S. Clark, R. Mady, P. Shah, and J. D. Kohtz The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator Genes & Dev., June 1, 2006; 20(11): 1470 - 1484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Wise and D. D. Pravtcheva Delayed Onset of Igf2-Induced Mammary Tumors in Igf2r Transgenic Mice Cancer Res., February 1, 2006; 66(3): 1327 - 1336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yamasaki, T. Kayashima, H. Soejima, A. Kinoshita, K.-i. Yoshiura, N. Matsumoto, T. Ohta, T. Urano, H. Masuzaki, T. Ishimaru, et al. Neuron-specific relaxation of Igf2r imprinting is associated with neuron-specific histone modifications and lack of its antisense transcript Air Hum. Mol. Genet., September 1, 2005; 14(17): 2511 - 2520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Arnaud, D. Monk, M. Hitchins, E. Gordon, W. Dean, C. V. Beechey, J. Peters, W. Craigen, M. Preece, P. Stanier, et al. Conserved methylation imprints in the human and mouse GRB10 genes with divergent allelic expression suggests differential reading of the same mark Hum. Mol. Genet., May 1, 2003; 12(9): 1005 - 1019. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Hassan Keys to the Hidden Treasures of the Mannose 6-Phosphate/Insulin-Like Growth Factor 2 Receptor Am. J. Pathol., January 1, 2003; 162(1): 3 - 6. [Full Text] [PDF]
|
|
|
|
 |
|
 B. Reinhart, M. Eljanne, and J. R. Chaillet Shared Role for Differentially Methylated Domains of Imprinted Genes Mol. Cell. Biol., April 1, 2002; 22(7): 2089 - 2098. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Burns and A. B. Hassan Cell survival and proliferation are modified by insulin-like growth factor 2 between days 9 and 10 of mouse gestation Development, October 1, 2001; 128(19): 3819 - 3830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zwart, F. Sleutels, A. Wutz, A. H. Schinkel, and D. P. Barlow Bidirectional action of the Igf2r imprint control element on upstream and downstream imprinted genes Genes & Dev., September 15, 2001; 15(18): 2361 - 2366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Killian, C. M. Nolan, A. A. Wylie, T. Li, T. H. Vu, A. R. Hoffman, and R. L. Jirtle Divergent evolution in M6P/IGF2R imprinting from the Jurassic to the Quaternary Hum. Mol. Genet., August 1, 2001; 10(17): 1721 - 1728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Sleutels and D. P. Barlow Investigation of Elements Sufficient To Imprint the Mouse Air Promoter Mol. Cell. Biol., August 1, 2001; 21(15): 5008 - 5017. [Abstract] [Full Text] [PDF]
|
|
