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

Eugene A. Berkowitz, Kim B. Seroogy, Joyce A. Schroeder, William E. Russell, Edward P. Evans, Richard F. Riedel, Harmony K. Phillips, Charles A. Harrison, David C. Lee, Noreen C. Luetteke

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

The spontaneous mouse waved 1 (wa1) mutation is allelic with the transforming growth factor α (TGF-α) gene and produces phenotypes similar to those of TGF-α knockout mice. Here, we show that TGF-α 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-α 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-α gene. TGF-α 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-α-null embryos display a significant delay in eyelid closure, although the eyes of most embryos fuse prior to birth. In situ hybridization localized TGF-α 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-α-deficient adult mice arise from premature exposure and trauma to open eyes during or following parturition.

Original languageEnglish (US)
Pages (from-to)1271-1282
Number of pages12
JournalCell Growth and Differentiation
Volume7
Issue number9
StatePublished - 1996

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Berkowitz, E. A., Seroogy, K. B., Schroeder, J. A., Russell, W. E., Evans, E. P., Riedel, R. F., Phillips, H. K., Harrison, C. A., Lee, D. C., & Luetteke, N. C. (1996). Characterization of the mouse transforming growth factor gene: Its expression during eyelid development and in waved 1 tissues. Cell Growth and Differentiation, 7(9), 1271-1282.