Abnormal fibrillin metabolism in bovine Marfan syndrome

Kathleen A. Potter, Yvonne Hoffman, Lynn Sakai, Peter H. Byers, Thomas E. Besser, Dianna M. Milewicz

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Bovine Marfan syndrome is a disorder that closely resembles human Marfan syndrome in its clinical signs and pathological lesions. The similarities between the human and bovine diseases suggest that similar metabolic defects could be responsible. Although indirect immunofluorescent assays for fibrillin in skin biopsies did not distinguish affected cattle from control animals, cultures of skin fibroblasts of affected animals were distinguished from normal, unrelated control animals and normal half-siblings on the basis of fibrillin staining. After 72 to 96 hours in culture, stained with anti-fibrillin monoclonal antibody 201, hyperconfluent fibroblast cultures of affected cattle had less immunoreactive fibrillin than control cultures, and the staining pattern was granular rather than fibrillar. Under similar culture conditions, normal bovine aortic smooth muscle cells produced large amounts of immunoreactive fibrillin, but smooth muscle cells from a single affected cow showed markedly less fibrillin staining. In pulse-chase metabolic labeling experiments with [35S]cysteine, dermal fibroblasts from 6 affected calves, incorporated far less fibrillin into the extracellular matrix than control cells. These findings are similar to those reported in human Marfan syndrome, and they suggest that the bovine Marfan syndrome, like the human disorder, is caused by a mutation in fibrillin, leading to defective microfibrillar synthesis.

Original languageEnglish (US)
Pages (from-to)803-810
Number of pages8
JournalAmerican Journal of Pathology
Volume142
Issue number3
StatePublished - Mar 1 1993
Externally publishedYes

Fingerprint

Marfan Syndrome
Fibroblasts
Staining and Labeling
Skin
Smooth Muscle Myocytes
Cattle Diseases
Fibrillins
Extracellular Matrix
Cysteine
Monoclonal Antibodies
Biopsy
Mutation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Potter, K. A., Hoffman, Y., Sakai, L., Byers, P. H., Besser, T. E., & Milewicz, D. M. (1993). Abnormal fibrillin metabolism in bovine Marfan syndrome. American Journal of Pathology, 142(3), 803-810.

Abnormal fibrillin metabolism in bovine Marfan syndrome. / Potter, Kathleen A.; Hoffman, Yvonne; Sakai, Lynn; Byers, Peter H.; Besser, Thomas E.; Milewicz, Dianna M.

In: American Journal of Pathology, Vol. 142, No. 3, 01.03.1993, p. 803-810.

Research output: Contribution to journalArticle

Potter, KA, Hoffman, Y, Sakai, L, Byers, PH, Besser, TE & Milewicz, DM 1993, 'Abnormal fibrillin metabolism in bovine Marfan syndrome', American Journal of Pathology, vol. 142, no. 3, pp. 803-810.
Potter KA, Hoffman Y, Sakai L, Byers PH, Besser TE, Milewicz DM. Abnormal fibrillin metabolism in bovine Marfan syndrome. American Journal of Pathology. 1993 Mar 1;142(3):803-810.
Potter, Kathleen A. ; Hoffman, Yvonne ; Sakai, Lynn ; Byers, Peter H. ; Besser, Thomas E. ; Milewicz, Dianna M. / Abnormal fibrillin metabolism in bovine Marfan syndrome. In: American Journal of Pathology. 1993 ; Vol. 142, No. 3. pp. 803-810.
@article{ba77c552b2d1411d899bec872e8d5942,
title = "Abnormal fibrillin metabolism in bovine Marfan syndrome",
abstract = "Bovine Marfan syndrome is a disorder that closely resembles human Marfan syndrome in its clinical signs and pathological lesions. The similarities between the human and bovine diseases suggest that similar metabolic defects could be responsible. Although indirect immunofluorescent assays for fibrillin in skin biopsies did not distinguish affected cattle from control animals, cultures of skin fibroblasts of affected animals were distinguished from normal, unrelated control animals and normal half-siblings on the basis of fibrillin staining. After 72 to 96 hours in culture, stained with anti-fibrillin monoclonal antibody 201, hyperconfluent fibroblast cultures of affected cattle had less immunoreactive fibrillin than control cultures, and the staining pattern was granular rather than fibrillar. Under similar culture conditions, normal bovine aortic smooth muscle cells produced large amounts of immunoreactive fibrillin, but smooth muscle cells from a single affected cow showed markedly less fibrillin staining. In pulse-chase metabolic labeling experiments with [35S]cysteine, dermal fibroblasts from 6 affected calves, incorporated far less fibrillin into the extracellular matrix than control cells. These findings are similar to those reported in human Marfan syndrome, and they suggest that the bovine Marfan syndrome, like the human disorder, is caused by a mutation in fibrillin, leading to defective microfibrillar synthesis.",
author = "Potter, {Kathleen A.} and Yvonne Hoffman and Lynn Sakai and Byers, {Peter H.} and Besser, {Thomas E.} and Milewicz, {Dianna M.}",
year = "1993",
month = "3",
day = "1",
language = "English (US)",
volume = "142",
pages = "803--810",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Abnormal fibrillin metabolism in bovine Marfan syndrome

AU - Potter, Kathleen A.

AU - Hoffman, Yvonne

AU - Sakai, Lynn

AU - Byers, Peter H.

AU - Besser, Thomas E.

AU - Milewicz, Dianna M.

PY - 1993/3/1

Y1 - 1993/3/1

N2 - Bovine Marfan syndrome is a disorder that closely resembles human Marfan syndrome in its clinical signs and pathological lesions. The similarities between the human and bovine diseases suggest that similar metabolic defects could be responsible. Although indirect immunofluorescent assays for fibrillin in skin biopsies did not distinguish affected cattle from control animals, cultures of skin fibroblasts of affected animals were distinguished from normal, unrelated control animals and normal half-siblings on the basis of fibrillin staining. After 72 to 96 hours in culture, stained with anti-fibrillin monoclonal antibody 201, hyperconfluent fibroblast cultures of affected cattle had less immunoreactive fibrillin than control cultures, and the staining pattern was granular rather than fibrillar. Under similar culture conditions, normal bovine aortic smooth muscle cells produced large amounts of immunoreactive fibrillin, but smooth muscle cells from a single affected cow showed markedly less fibrillin staining. In pulse-chase metabolic labeling experiments with [35S]cysteine, dermal fibroblasts from 6 affected calves, incorporated far less fibrillin into the extracellular matrix than control cells. These findings are similar to those reported in human Marfan syndrome, and they suggest that the bovine Marfan syndrome, like the human disorder, is caused by a mutation in fibrillin, leading to defective microfibrillar synthesis.

AB - Bovine Marfan syndrome is a disorder that closely resembles human Marfan syndrome in its clinical signs and pathological lesions. The similarities between the human and bovine diseases suggest that similar metabolic defects could be responsible. Although indirect immunofluorescent assays for fibrillin in skin biopsies did not distinguish affected cattle from control animals, cultures of skin fibroblasts of affected animals were distinguished from normal, unrelated control animals and normal half-siblings on the basis of fibrillin staining. After 72 to 96 hours in culture, stained with anti-fibrillin monoclonal antibody 201, hyperconfluent fibroblast cultures of affected cattle had less immunoreactive fibrillin than control cultures, and the staining pattern was granular rather than fibrillar. Under similar culture conditions, normal bovine aortic smooth muscle cells produced large amounts of immunoreactive fibrillin, but smooth muscle cells from a single affected cow showed markedly less fibrillin staining. In pulse-chase metabolic labeling experiments with [35S]cysteine, dermal fibroblasts from 6 affected calves, incorporated far less fibrillin into the extracellular matrix than control cells. These findings are similar to those reported in human Marfan syndrome, and they suggest that the bovine Marfan syndrome, like the human disorder, is caused by a mutation in fibrillin, leading to defective microfibrillar synthesis.

UR - http://www.scopus.com/inward/record.url?scp=0027761181&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027761181&partnerID=8YFLogxK

M3 - Article

VL - 142

SP - 803

EP - 810

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 3

ER -