Identification and characterization of a novel, evolutionary conserved gene disrupted by the murine Hβ58 embryonic lethal transgene insertion

James J. Lee, Glenn Radice, Christopher P. Perkins, Frank Costantini

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

The Hβ58 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 Hβ58 locus, whose disruption appears to be responsible for the mutant phenotype. The wild-type Hβ58 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 Hβ58 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 Hβ58 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 Hβ58 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 Hβ58 cDNA clones revealed no homology between the 38×103 Mr Hβ58 protein and other known proteins. However, the Hβ58 gene displayed extremely strong conservation between mammals and birds (>96% amino acid identity), although it appeared less conserved in amphibians and invertebrates.

Original languageEnglish (US)
Pages (from-to)277-288
Number of pages12
JournalDevelopment
Volume115
Issue number1
StatePublished - May 1992
Externally publishedYes

Fingerprint

Transgenes
Genes
Endoderm
Ectoderm
Messenger RNA
Mutation
Embryonic and Fetal Development
Amphibians
Invertebrates
Transgenic Mice
Oocytes
Birds
Embryonic Development
In Situ Hybridization
Ovum
Sequence Analysis
Mammals
Exons
Proteins
Embryonic Structures

Keywords

  • Evolutionary conservation
  • Hβ58
  • In situ hybridization
  • Insertional mutation
  • Mouse embryo
  • Transgenic mice

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Identification and characterization of a novel, evolutionary conserved gene disrupted by the murine Hβ58 embryonic lethal transgene insertion. / Lee, James J.; Radice, Glenn; Perkins, Christopher P.; Costantini, Frank.

In: Development, Vol. 115, No. 1, 05.1992, p. 277-288.

Research output: Contribution to journalArticle

Lee, James J. ; Radice, Glenn ; Perkins, Christopher P. ; Costantini, Frank. / Identification and characterization of a novel, evolutionary conserved gene disrupted by the murine Hβ58 embryonic lethal transgene insertion. In: Development. 1992 ; Vol. 115, No. 1. pp. 277-288.
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