Transinhibition of C1 inhibitor synthesis in type I hereditary angioneurotic edema.

Kramer, J.; Rosen, Fred S.; Colten, Harvey R.; Rajczy, Katalin; Strunk, Robert C.

doi:10.1172/jci116290

Cited by 57 publications

(35 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Patients with HAE catabolize C1-INH faster than normal subjects, 16 but concomitant downregulation of the normal allele may also occur, at least with some mutations. [17][18][19] Most mutations that cause HAE are point mutations resulting in single amino acid substitutions. 10 Independent families rarely possess identical mutations.…”

Section: The Genetics Of Hereditary Angioedemamentioning

confidence: 99%

Pathophysiology of Hereditary Angioedema

Caccia

Suffritti

Cicardi

2014

Pediatric Allergy, Immunology, and Pulmonology

View full text Add to dashboard Cite

Section: The Genetics Of Hereditary Angioedemamentioning

confidence: 99%

Pathophysiology of Hereditary Angioedema

Caccia

Suffritti

Cicardi

2014

Pediatric Allergy, Immunology, and Pulmonology

View full text Add to dashboard Cite

“…It was first thought that catabolism of the normal protein causes this reduction in activity (40). However, it has also been suggested that the mutant C1INH may transinhibit the normal gene (41) or there may be decreased secretion of C1INH (33,42). Type II HAE is evident in 15% of HAE patients and is characterized by normal or raised antigenic levels of C1INH that have diminished function (43).…”

Section: Introductionmentioning

confidence: 99%

A Review of the Reported Defects in the Human C1 Esterase Inhibitor Gene Producing Hereditary Angioedema Including Four New Mutations

Bowen

Hawk

Sibunka

et al. 2001

Clinical Immunology

View full text Add to dashboard Cite

“…The structural abnormalities of C1INH gene in patients with HAE type I are very heterogeneous, including point mutations, deletions and insertions that lead to an unstable and easily degraded mRNA, and an apparent failure to synthesise or secrete the C1INH protein (8)(9)(10). However, mutations abolishing the physiological stop codon are rare, and such mutations have not been reported as a cause of C1INH deficiency.…”

Section: Resultsmentioning

confidence: 99%

A novel mutation in exon 8 of C1 inhibitor (C1INH) gene leads to abolish its physiological stop codon in a large Chinese family with hereditary angioedema type I

Wei

Liu

et al. 2012

Experimental Dermatology

View full text Add to dashboard Cite

tissue, it was not possible to analyse brain metastasis using this method. However, anti-Trp2 staining of the brain showed no evidence of disseminated melanoma cells within neuronal tissue (data not shown). We further analysed the bone marrow of Grm1-transgenic animals for expression of the Grm1 receptor through qRT-PCR analysis. We detected Grm1 mRNA expression within the bone marrow of Tg(Grm1)EPv-transgenic mice showing marked primary tumor growth (Fig. 2c, B.m. Grm1/185 d). In contrast, Grm1 expression was completely absent in the bone marrow of normal C57Bl/6 mice (Fig. 2c). Interestingly, Tg (Grm1)EPv animals with slight melanoma growth also showed Grm1 mRNA expression but at significantly lower levels compared with distinct tumor-bearing mice (Fig. 2c, B.m. Grm1/ 125 d). ConclusionsWe demonstrate that the Tg(Grm1)EPv-transgenic mouse model reveals more extensive metastasis into proximal and distant organs than previously assumed. In addition to the described pigmented melanoma cells in the lymph nodes (3), we detected high numbers of disseminated Grm1-positive cells within the lymphatic organs and in the lung and liver. Most importantly, the majority of Grm1-expressing cells within distant organs were non-pigmented. Furthermore, Grm1 expression was detected in the bone marrow even at early tumor stages. Therefore, we conclude that the dissemination of melanoma cells in the Tg(Grm1)EPv mouse model occurs early and is associated with phenotypic alterations during advanced metastasis. Our immunohistochemical analyses indicate that disseminating cells reverse the later differentiation steps: indeed, although Trp2 expression was still detectable, most of the cells lose melanin synthesis in distant organs. These data clearly indicate that melanoma metastasis differs between the two Grm1-transgenic mouse strains TG3 and Tg(Grm1)EPv (3). Thus, the aim of further studies will be to investigate these underlying molecular differences to obtain new insights into melanoma metastasis. Because phenotypic changes during metastasis are also frequently observed in human melanoma (11,12), the Tg(Grm1) EPv mouse line represents an appropriate animal model to investigate the mechanisms of melanoma initiation and spontaneous metastasis in the human disease. AcknowledgementsThe authors thank Mrs Simone Kaufmann, Mrs Martina Waeber and Mr Rudi Jung for excellent technical assistance. The study was supported by the Melanoma Research Network (German Cancer Aid). A.K.B. designed the study, analysed and interpreted data and wrote the manuscript. S.S. performed the experiments, analysed data and wrote the manuscript. S.C. and J.C.B. analysed and interpreted data and were involved in writing the article. This work complies with the ethical policies of Experimental Dermatology. Conflict of interestThe authors declare no conflict of interests. Supporting InformationAdditional Supporting Information may be found in the online version of this article: Data S1. Materials and methods. Figure S1. Immunohistochemical analysis to identify mel...

show abstract

Transinhibition of C1 inhibitor synthesis in type I hereditary angioneurotic edema.

Abstract: To ascertain the mechanism for decreased synthesis ofC1 inhibitor (Cl INH) Clin. Invest. 1993.91:1258-1262

Cited by 57 publications

References 16 publications

Pathophysiology of Hereditary Angioedema

Pathophysiology of Hereditary Angioedema

A Review of the Reported Defects in the Human C1 Esterase Inhibitor Gene Producing Hereditary Angioedema Including Four New Mutations

A novel mutation in exon 8 of C1 inhibitor (C1INH) gene leads to abolish its physiological stop codon in a large Chinese family with hereditary angioedema type I

Contact Info

Product

Resources

About