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Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis.

Publication ,  Journal Article
Chen, B; Bronson, RT; Klaman, LD; Hampton, TG; Wang, JF; Green, PJ; Magnuson, T; Douglas, PS; Morgan, JP; Neel, BG
Published in: Nat Genet
March 2000

Atrioventricular and semilunar valve abnormalities are common birth defects, but how cardiac valvulogenesis is directed remains largely unknown. During studies of genetic interaction between Egfr, encoding the epidermal growth factor receptor, and Ptpn11, encoding the protein-tyrosine-phosphatase Shp2, we discovered that Egfr is required for semilunar, but not atrioventricular, valve development. Although unnoticed in earlier studies, mice homozygous for the hypomorphic Egfr allele waved-2 (Egfrwa2/wa2) exhibit semilunar valve enlargement resulting from over-abundant mesenchymal cells. Egfr-/- mice (CD1 background) have similar defects. The penetrance and severity of the defects in Egfrwa2/wa2 mice are enhanced by heterozygosity for a targeted mutation of exon 2 of Ptpn11 (ref. 3). Compound (Egfrwa2/wa2:Ptpn11+/-) mutant mice also show premature lethality. Electrocardiography, echocardiography and haemodynamic analyses showed that affected mice develop aortic stenosis and regurgitation. Our results identify the Egfr and Shp2 as components of a growth-factor signalling pathway required specifically for semilunar valvulogenesis, support the hypothesis that Shp2 is required for Egfr signalling in vivo, and provide an animal model for aortic valve disease.

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Published In

Nat Genet

DOI

ISSN

1061-4036

Publication Date

March 2000

Volume

24

Issue

3

Start / End Page

296 / 299

Location

United States

Related Subject Headings

  • Ventricular Dysfunction, Left
  • Sequence Deletion
  • Pulmonary Valve
  • Protein Tyrosine Phosphatases
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Mesoderm
 

Citation

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Chen, B., Bronson, R. T., Klaman, L. D., Hampton, T. G., Wang, J. F., Green, P. J., … Neel, B. G. (2000). Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis. Nat Genet, 24(3), 296–299. https://doi.org/10.1038/73528
Chen, B., R. T. Bronson, L. D. Klaman, T. G. Hampton, J. F. Wang, P. J. Green, T. Magnuson, P. S. Douglas, J. P. Morgan, and B. G. Neel. “Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis.Nat Genet 24, no. 3 (March 2000): 296–99. https://doi.org/10.1038/73528.
Chen B, Bronson RT, Klaman LD, Hampton TG, Wang JF, Green PJ, et al. Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis. Nat Genet. 2000 Mar;24(3):296–9.
Chen, B., et al. “Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis.Nat Genet, vol. 24, no. 3, Mar. 2000, pp. 296–99. Pubmed, doi:10.1038/73528.
Chen B, Bronson RT, Klaman LD, Hampton TG, Wang JF, Green PJ, Magnuson T, Douglas PS, Morgan JP, Neel BG. Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis. Nat Genet. 2000 Mar;24(3):296–299.

Published In

Nat Genet

DOI

ISSN

1061-4036

Publication Date

March 2000

Volume

24

Issue

3

Start / End Page

296 / 299

Location

United States

Related Subject Headings

  • Ventricular Dysfunction, Left
  • Sequence Deletion
  • Pulmonary Valve
  • Protein Tyrosine Phosphatases
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Mesoderm