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 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 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Transforming Growth Factors
Eyelids
Gene Expression
Parturition
Knockout Mice
Mutation
Genes
Embryonic Structures
Messenger RNA
Corneal Epithelium
Chromosomes, Human, Pair 6
Pulsed Field Gel Electrophoresis
Epidermal Growth Factor Receptor
In Situ Hybridization
Epithelium
Phenotype
Pregnancy
Wounds and Injuries

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Berkowitz, E. A., Seroogy, K. B., Schroeder, J., Russell, W. E., Evans, E. P., Riedel, R. F., ... 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.

Characterization of the mouse transforming growth factor gene : Its expression during eyelid development and in waved 1 tissues. / Berkowitz, Eugene A.; Seroogy, Kim B.; Schroeder, Joyce; Russell, William E.; Evans, Edward P.; Riedel, Richard F.; Phillips, Harmony K.; Harrison, Charles A.; Lee, David C.; Luetteke, Noreen C.

In: Cell Growth and Differentiation, Vol. 7, No. 9, 1996, p. 1271-1282.

Research output: Contribution to journalArticle

Berkowitz, EA, Seroogy, KB, Schroeder, J, Russell, WE, Evans, EP, Riedel, RF, Phillips, HK, Harrison, CA, Lee, DC & Luetteke, NC 1996, 'Characterization of the mouse transforming growth factor gene: Its expression during eyelid development and in waved 1 tissues', Cell Growth and Differentiation, vol. 7, no. 9, pp. 1271-1282.
Berkowitz, Eugene A. ; Seroogy, Kim B. ; Schroeder, Joyce ; Russell, William E. ; Evans, Edward P. ; Riedel, Richard F. ; Phillips, Harmony K. ; Harrison, Charles A. ; Lee, David C. ; Luetteke, Noreen C. / Characterization of the mouse transforming growth factor gene : Its expression during eyelid development and in waved 1 tissues. In: Cell Growth and Differentiation. 1996 ; Vol. 7, No. 9. pp. 1271-1282.
@article{89a970a36fb946d48d9592dfcbf1941c,
title = "Characterization of the mouse transforming growth factor gene: Its expression during eyelid development and in waved 1 tissues",
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.",
author = "Berkowitz, {Eugene A.} and Seroogy, {Kim B.} and Joyce Schroeder and Russell, {William E.} and Evans, {Edward P.} and Riedel, {Richard F.} and Phillips, {Harmony K.} and Harrison, {Charles A.} and Lee, {David C.} and Luetteke, {Noreen C.}",
year = "1996",
language = "English (US)",
volume = "7",
pages = "1271--1282",
journal = "Molecular Cancer Research",
issn = "1541-7786",
publisher = "American Association for Cancer Research Inc.",
number = "9",

}

TY - JOUR

T1 - Characterization of the mouse transforming growth factor gene

T2 - Its expression during eyelid development and in waved 1 tissues

AU - Berkowitz, Eugene A.

AU - Seroogy, Kim B.

AU - Schroeder, Joyce

AU - Russell, William E.

AU - Evans, Edward P.

AU - Riedel, Richard F.

AU - Phillips, Harmony K.

AU - Harrison, Charles A.

AU - Lee, David C.

AU - Luetteke, Noreen C.

PY - 1996

Y1 - 1996

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=10244252796&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10244252796&partnerID=8YFLogxK

M3 - Article

C2 - 8877107

AN - SCOPUS:10244252796

VL - 7

SP - 1271

EP - 1282

JO - Molecular Cancer Research

JF - Molecular Cancer Research

SN - 1541-7786

IS - 9

ER -