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A mouse model for hereditary hemorrhagic telangiectasia (HHT) type 2.

Publication ,  Journal Article
Srinivasan, S; Hanes, MA; Dickens, T; Porteous, MEM; Oh, SP; Hale, LP; Marchuk, DA
Published in: Hum Mol Genet
March 1, 2003

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant disorder characterized by the age-dependent development of focal arteriovenous malformations and telangiectases. HHT type 2 is caused by loss of function mutations in activin receptor-like kinase 1 (ACVRL1 or ALK1). However, the factors that initiate lesion formation and those that influence disease progression remain unknown. Because heterozygous mice contain the appropriate genotype for an animal model of this disorder, mice heterozygous for a loss-of-function mutation in Acvrl1 were carefully examined for an HHT-like phenotype. These mice developed age-dependent vascular lesions in the skin, extremities, oral cavity and in the internal organs (lung, liver, intestine, spleen and brain), similar to those seen in HHT patients. Major histopathological features of the lesions included thin-walled dilated vessels in close proximity to each other, hemorrhage and fibrosis. Similar to HHT patients, the mice also exhibited gastrointestinal bleeding, as evidenced by positive fecal occult blood tests. An Acvrl1(+/-) mouse with profound liver involvement also displayed a secondary cardiac phenotype, similar to that observed in human patients. The similarity of affected organs, age-dependent penetrance, histological similarity of the lesions and recapitulation of a secondary phenotype suggest that the Acvrl1(+/-) mice are an appropriate animal model for the identification of additional genetic and environmental factors that cause pathology in HHT type 2 patients. In addition, studies utilizing this animal model can yield valuable information on the role of ALK1 in maintenance of adult vascular architecture including arteriovenous identity.

Duke Scholars

Published In

Hum Mol Genet

DOI

ISSN

0964-6906

Publication Date

March 1, 2003

Volume

12

Issue

5

Start / End Page

473 / 482

Location

England

Related Subject Headings

  • Telangiectasia, Hereditary Hemorrhagic
  • Spleen
  • Skin Abnormalities
  • Mice
  • Male
  • Lung
  • Liver
  • Limb Deformities, Congenital
  • Humans
  • Genetics & Heredity
 

Citation

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MLA
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Srinivasan, S., Hanes, M. A., Dickens, T., Porteous, M. E. M., Oh, S. P., Hale, L. P., & Marchuk, D. A. (2003). A mouse model for hereditary hemorrhagic telangiectasia (HHT) type 2. Hum Mol Genet, 12(5), 473–482. https://doi.org/10.1093/hmg/ddg050
Srinivasan, Sudha, Martha A. Hanes, Tayeashai Dickens, Mary E. M. Porteous, S Paul Oh, Laura P. Hale, and Douglas A. Marchuk. “A mouse model for hereditary hemorrhagic telangiectasia (HHT) type 2.Hum Mol Genet 12, no. 5 (March 1, 2003): 473–82. https://doi.org/10.1093/hmg/ddg050.
Srinivasan S, Hanes MA, Dickens T, Porteous MEM, Oh SP, Hale LP, et al. A mouse model for hereditary hemorrhagic telangiectasia (HHT) type 2. Hum Mol Genet. 2003 Mar 1;12(5):473–82.
Srinivasan, Sudha, et al. “A mouse model for hereditary hemorrhagic telangiectasia (HHT) type 2.Hum Mol Genet, vol. 12, no. 5, Mar. 2003, pp. 473–82. Pubmed, doi:10.1093/hmg/ddg050.
Srinivasan S, Hanes MA, Dickens T, Porteous MEM, Oh SP, Hale LP, Marchuk DA. A mouse model for hereditary hemorrhagic telangiectasia (HHT) type 2. Hum Mol Genet. 2003 Mar 1;12(5):473–482.
Journal cover image

Published In

Hum Mol Genet

DOI

ISSN

0964-6906

Publication Date

March 1, 2003

Volume

12

Issue

5

Start / End Page

473 / 482

Location

England

Related Subject Headings

  • Telangiectasia, Hereditary Hemorrhagic
  • Spleen
  • Skin Abnormalities
  • Mice
  • Male
  • Lung
  • Liver
  • Limb Deformities, Congenital
  • Humans
  • Genetics & Heredity