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Characterization of the mouse transforming growth factor alpha gene: its expression during eyelid development and in waved 1 tissues.

Publication ,  Journal Article
Berkowitz, EA; Seroogy, KB; Schroeder, JA; Russell, WE; Evans, EP; Riedel, RF; Phillips, HK; Harrison, CA; Lee, DC; Luetteke, NC
Published in: Cell Growth Differ
September 1996

The spontaneous mouse waved 1 (wa1) mutation is allelic with the transforming growth factor alpha (TGF-alpha) gene and produces phenotypes similar to those of TGF-alpha knockout mice. Here, we show that TGF-alpha mRNA and protein levels are measurable in wa1 tissues but reduced 5- to 30-fold relative to wild type. Because the wa1-coding sequence is identical to that of the normal mRNA, wa1 is not a null mutation. Nuclear run-on analyses revealed decreased transcription of the TGF-alpha gene in wa1 tissues, but the sequence of a 3.2-kb 5' flanking fragment containing the promoter was unaltered. Moreover, pulsed field gel electrophoresis analysis did not reveal alterations within 750 kb upstream or 350 kb downstream of the gene, and chromosome 6 was karyotypically normal. Hence, we speculate that the wa1 mutation may be subtle and/or reside at a greater distance from the TGF-alpha gene. TGF-alpha deficiency elicits a spectrum of variably penetrant eye anomalies in wa1 and knockout mice that are associated with open eyes at birth. We found that late-gestation wa1 and TGF-alpha-null embryos display a significant delay in eyelid closure, although the eyes of most embryos fuse prior to birth. In situ hybridization localized TGF-alpha expression to the advancing margins of the eyelid epithelium and epidermal growth factor receptor expression throughout the eyelid and corneal epithelia. These results suggest that eye problems observed in TGF-alpha-deficient adult mice arise from premature exposure and trauma to open eyes during or following parturition.

Duke Scholars

Published In

Cell Growth Differ

ISSN

1044-9523

Publication Date

September 1996

Volume

7

Issue

9

Start / End Page

1271 / 1282

Location

United States

Related Subject Headings

  • Transforming Growth Factor alpha
  • Transcription, Genetic
  • Sequence Analysis, DNA
  • RNA, Messenger
  • Promoter Regions, Genetic
  • Organ Specificity
  • Oncology & Carcinogenesis
  • Mutation
  • Molecular Sequence Data
  • Mice, Mutant Strains
 

Citation

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Berkowitz, E. A., Seroogy, K. B., Schroeder, J. A., Russell, W. E., Evans, E. P., Riedel, R. F., … Luetteke, N. C. (1996). Characterization of the mouse transforming growth factor alpha gene: its expression during eyelid development and in waved 1 tissues. Cell Growth Differ, 7(9), 1271–1282.
Berkowitz, E. A., K. B. Seroogy, J. A. Schroeder, W. E. Russell, E. P. Evans, R. F. Riedel, H. K. Phillips, C. A. Harrison, D. C. Lee, and N. C. Luetteke. “Characterization of the mouse transforming growth factor alpha gene: its expression during eyelid development and in waved 1 tissues.Cell Growth Differ 7, no. 9 (September 1996): 1271–82.
Berkowitz EA, Seroogy KB, Schroeder JA, Russell WE, Evans EP, Riedel RF, et al. Characterization of the mouse transforming growth factor alpha gene: its expression during eyelid development and in waved 1 tissues. Cell Growth Differ. 1996 Sep;7(9):1271–82.
Berkowitz, E. A., et al. “Characterization of the mouse transforming growth factor alpha gene: its expression during eyelid development and in waved 1 tissues.Cell Growth Differ, vol. 7, no. 9, Sept. 1996, pp. 1271–82.
Berkowitz EA, Seroogy KB, Schroeder JA, Russell WE, Evans EP, Riedel RF, Phillips HK, Harrison CA, Lee DC, Luetteke NC. Characterization of the mouse transforming growth factor alpha gene: its expression during eyelid development and in waved 1 tissues. Cell Growth Differ. 1996 Sep;7(9):1271–1282.

Published In

Cell Growth Differ

ISSN

1044-9523

Publication Date

September 1996

Volume

7

Issue

9

Start / End Page

1271 / 1282

Location

United States

Related Subject Headings

  • Transforming Growth Factor alpha
  • Transcription, Genetic
  • Sequence Analysis, DNA
  • RNA, Messenger
  • Promoter Regions, Genetic
  • Organ Specificity
  • Oncology & Carcinogenesis
  • Mutation
  • Molecular Sequence Data
  • Mice, Mutant Strains