Development, Vol 115, Issue 1 277-288, Copyright © 1992 by Company of Biologists

JOURNAL ARTICLES

Identification and characterization of a novel, evolutionarily conserved gene disrupted by the murine H beta 58 embryonic lethal transgene insertion

JJ Lee, G Radice, CP Perkins and F Costantini
Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032.

The H beta 58 transgenic mouse line carries a recessive insertional mutation that results in developmental abnormalities beginning at day 7.5 p.c. and embryonic arrest at about day 9.5. In this paper, we describe the characterization of a novel gene encoded at the H beta 58 locus, whose disruption appears to be responsible for the mutant phenotype. The wild-type H beta 58 gene encodes a single 2.7 kb mRNA during embryonic and fetal development, and in many adult somatic tissues. In the mutant locus, this transcription unit is split by the transgene insertion, and one of its coding exons is deleted. Consistent with the physical disruption of the gene, the level of the H beta 58 mRNA in heterozygous mutant mouse tissues was half the normal level, indicating that the mutant allele fails to encode a stable mRNA. In situ hybridization studies revealed that expression of the wild-type H beta 58 gene begins in the oocyte, and continues throughout pre- and post-implantation embryogenesis, despite the fact that homozygous mutant embryos develop successfully through the egg cylinder stage (day 6.5 p.c.). In the early post-implantation embryo, expression of the normal H beta 58 gene is relatively low in the embryonic ectoderm, the tissue displaying the earliest phenotypic effects of the mutation, and highest in the visceral endoderm. We therefore propose that the effects of the mutation on the embryonic ectoderm may be exerted indirectly, via the visceral endoderm. Sequence analysis of H beta 58 cDNA clones revealed no homology between the 38 x 10(3) M(r) H beta 58 protein and other known proteins. However, the H beta 58 gene displayed extremely strong conservation between mammals and birds (greater than 96% amino acid identity), although it appeared less conserved in amphibians and invertebrates.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. Muhammad, I. Flores, H. Zhang, R. Yu, A. Staniszewski, E. Planel, M. Herman, L. Ho, R. Kreber, L. S. Honig, et al. Retromer deficiency observed in Alzheimer's disease causes hippocampal dysfunction, neurodegeneration, and A{beta} accumulation PNAS, May 20, 2008; 105(20): 7327 - 7332. [Abstract] [Full Text] [PDF]

				R. Rojas, S. Kametaka, C. R. Haft, and J. S. Bonifacino Interchangeable but Essential Functions of SNX1 and SNX2 in the Association of Retromer with Endosomes and the Trafficking of Mannose 6-Phosphate Receptors Mol. Cell. Biol., February 1, 2007; 27(3): 1112 - 1124. [Abstract] [Full Text] [PDF]

				N. M. Lewandowski and S. A. Small Brain Microarray: Finding Needles in Molecular Haystacks J. Neurosci., November 9, 2005; 25(45): 10341 - 10346. [Full Text] [PDF]

				C. T. Griffin, J. Trejo, and T. Magnuson Genetic evidence for a mammalian retromer complex containing sorting nexins 1 and 2 PNAS, October 18, 2005; 102(42): 15173 - 15177. [Abstract] [Full Text] [PDF]

				S. Strope, R. Rivi, T. Metzger, K. Manova, and E. Lacy Mouse amnionless, which is required for primitive streak assembly, mediates cell-surface localization and endocytic function of cubilin on visceral endoderm and kidney proximal tubules Development, October 1, 2004; 131(19): 4787 - 4795. [Abstract] [Full Text] [PDF]

				M. N.J. Seaman Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer J. Cell Biol., April 12, 2004; 165(1): 111 - 122. [Abstract] [Full Text] [PDF]

				S. A. Cormier, S. Yuan, J. R. Crosby, C. A. Protheroe, D. M. Dimina, E. M. Hines, N. A. Lee, and J. J. Lee TH2-Mediated Pulmonary Inflammation Leads to the Differential Expression of Ribonuclease Genes by Alveolar Macrophages Am. J. Respir. Cell Mol. Biol., December 1, 2002; 27(6): 678 - 687. [Abstract] [Full Text] [PDF]

				D. G. Schwarz, C. T. Griffin, E. A. Schneider, D. Yee, and T. Magnuson Genetic Analysis of Sorting Nexins 1 and 2 Reveals a Redundant and Essential Function in Mice Mol. Biol. Cell, October 1, 2002; 13(10): 3588 - 3600. [Abstract] [Full Text] [PDF]

				J. V. Reddy and M. N.J. Seaman Vps26p, a Component of Retromer, Directs the Interactions of Vps35p in Endosome-to-Golgi Retrieval Mol. Biol. Cell, October 1, 2001; 12(10): 3242 - 3256. [Abstract] [Full Text] [PDF]

				V. Rider, S. R. Jones, R. T. Foster, and K. Imakawa Changes in the Temporal and Spatial Expression of H{beta}58 During Formation and Maturation of the Chorioallantoic Placenta in the Rat Biol Reprod, December 1, 2000; 63(6): 1735 - 1746. [Abstract] [Full Text]

				Y. G. Yueh, D. P. Gardner, and C. Kappen Evidence for regulation of cartilage differentiation by the homeobox gene Hoxc-8 PNAS, August 18, 1998; 95(17): 9956 - 9961. [Abstract] [Full Text] [PDF]

				M. N.J. Seaman, J. Michael McCaffery, and S. D. Emr A Membrane Coat Complex Essential for Endosome-to-Golgi Retrograde Transport in Yeast J. Cell Biol., August 10, 1998; 142(3): 665 - 681. [Abstract] [Full Text] [PDF]

				C. Sirard, J. L. de la Pompa, A. Elia, A. Itie, C. Mirtsos, A. Cheung, S. Hahn, A. Wakeham, L. Schwartz, S. E. Kern, et al. The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo Genes & Dev., January 1, 1998; 12(1): 107 - 119. [Abstract] [Full Text]

				J. J. Lee, M. P. McGarry, S. C. Farmer, K. L. Denzler, K. A. Larson, P. E. Carrigan, I. E. Brenneise, M. A. Horton, A. Haczku, E. W. Gelfand, et al. Interleukin-5 Expression in the Lung Epithelium of Transgenic Mice Leads to Pulmonary Changes Pathognomonic of Asthma J. Exp. Med., June 16, 1997; 185(12): 2143 - 2156. [Abstract] [Full Text] [PDF]

				S. Duncan, A Nagy, and W Chan Murine gastrulation requires HNF-4 regulated gene expression in the visceral endoderm: tetraploid rescue of Hnf-4(-/-) embryos Development, January 1, 1997; 124(2): 279 - 287. [Abstract] [PDF]

				C Soudais, M Bielinska, M Heikinheimo, C. MacArthur, N Narita, J. Saffitz, M. Simon, J. Leiden, and D. Wilson Targeted mutagenesis of the transcription factor GATA-4 gene in mouse embryonic stem cells disrupts visceral endoderm differentiation in vitro Development, January 11, 1995; 121(11): 3877 - 3888. [Abstract] [PDF]

				W S Chen, K Manova, D C Weinstein, S A Duncan, A S Plump, V R Prezioso, R F Bachvarova, and J E Darnell Disruption of the HNF-4 gene, expressed in visceral endoderm, leads to cell death in embryonic ectoderm and impaired gastrulation of mouse embryos. Genes & Dev., October 15, 1994; 8(20): 2466 - 2477. [Abstract] [PDF]

				A K Bachhawat, J Suhan, and E W Jones The yeast homolog of H < beta > 58, a mouse gene essential for embryogenesis, performs a role in the delivery of proteins to the vacuole. Genes & Dev., June 15, 1994; 8(12): 1379 - 1387. [Abstract] [PDF]

				J DeGregori, A Russ, H von Melchner, H Rayburn, P Priyaranjan, N A Jenkins, N G Copeland, and H E Ruley A murine homolog of the yeast RNA1 gene is required for postimplantation development. Genes & Dev., February 1, 1994; 8(3): 265 - 276. [Abstract] [PDF]

				F. Conlon, K. Lyons, N Takaesu, K. Barth, A Kispert, B Herrmann, and E. Robertson A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse Development, January 7, 1994; 120(7): 1919 - 1928. [Abstract] [PDF]