東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

Expression of a human amyloidogenic ...

Ward, Jennifer Ellis.

Linked to FindBook

Google Book

Amazon

博客來

Expression of a human amyloidogenic immunoglobulin light chain produces renal and cardiac disease in mice.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Expression of a human amyloidogenic immunoglobulin light chain produces renal and cardiac disease in mice./
Author:	Ward, Jennifer Ellis.
Description:	252 p.
Notes:	Source: Dissertation Abstracts International, Volume: 66-11, Section: B, page: 5830.
Contained By:	Dissertation Abstracts International66-11B.
Subject:	Biology, Molecular. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3194777
ISBN:	9780542396601

Expression of a human amyloidogenic immunoglobulin light chain produces renal and cardiac disease in mice.
Ward, Jennifer Ellis.

Expression of a human amyloidogenic immunoglobulin light chain produces renal and cardiac disease in mice. - 252 p.

Source: Dissertation Abstracts International, Volume: 66-11, Section: B, page: 5830.

Thesis (Ph.D.)--Boston University, 2006.

Primary systemic AL amyloidosis is caused by clonal bone marrow plasma cells that secrete an immunoglobulin whose light chain (LC) forms amyloid. Amyloid is a general term for misfolded proteins that polymerize and form fibrils with a cross beta-sheet structure. In the systemic amyloidoses, these fibrils deposit extracellularly in various target organs, particularly the heart and kidneys in AL amyloidosis. Recent evidence has challenged the dogma that tissue damage is solely the result of amyloid fibril deposition. To examine whether amyloidogenic human immunoglobulin light chains may cause acute toxic effects prior to the development of fibrillar tissue deposits in vivo, amyloidogenic LC-expressing cell lines were generated and transplanted into mice. A lambda6 LC gene was cloned from a patient with aggressive multi-organ AL amyloidosis and stably expressed in SP2/0 plasmacytoma cells, which were injected into syngeneic Balb/c and RAG-/- mice. Four to six weeks later, echocardiograms were performed and the mice were euthanized and serum, urine, and tissues were collected. Mice injected with LC-producing cells had detectable circulating human LC in their serum and some mice excreted LC and albumin in the urine, whereas mice injected with untransfected cells did not. In the kidney, there were amorphous protein deposits and early glomerulopathy by electron microscopy in two mice examined, but no mature fibril deposition. These mice had bradycardia and upregulation of the cell stress marker heme oxygenase-1 in the heart. Therefore, short-term expression of human amyloidogenic LC in mice in vivo produces alterations in kidney and heart function prior to the development of fibrillar deposits. However, the tumor model is unsuitable for long-term studies because of overgrowth of the plasmacytoma cells. To circumvent this problem, a transgenic model was developed in which the same lambda6 LC gene was expressed using a CMV promoter. In three transgenic lines, LC is expressed in epithelial cells and found in serum and urine. Thus, these mice will be useful for the study of accessory factors in amyloidogenesis and for the development of novel therapeutic approaches.

ISBN: 9780542396601Subjects--Topical Terms:

1017719
Biology, Molecular.

Expression of a human amyloidogenic immunoglobulin light chain produces renal and cardiac disease in mice.
LDR:03136nmm 2200289 4500 001 1825401
005 20061211074620.5
008 130610s2006 eng d
020 $a 9780542396601
035 $a (UnM)AAI3194777
035 $a AAI3194777
040 $a UnM $c UnM
100 1 $a Ward, Jennifer Ellis. $3 1914414
245 1 0 $a Expression of a human amyloidogenic immunoglobulin light chain produces renal and cardiac disease in mice.
300 $a 252 p.
500 $a Source: Dissertation Abstracts International, Volume: 66-11, Section: B, page: 5830.
500 $a Major Professor: David C. Seldin.
502 $a Thesis (Ph.D.)--Boston University, 2006.
520 $a Primary systemic AL amyloidosis is caused by clonal bone marrow plasma cells that secrete an immunoglobulin whose light chain (LC) forms amyloid. Amyloid is a general term for misfolded proteins that polymerize and form fibrils with a cross beta-sheet structure. In the systemic amyloidoses, these fibrils deposit extracellularly in various target organs, particularly the heart and kidneys in AL amyloidosis. Recent evidence has challenged the dogma that tissue damage is solely the result of amyloid fibril deposition. To examine whether amyloidogenic human immunoglobulin light chains may cause acute toxic effects prior to the development of fibrillar tissue deposits in vivo, amyloidogenic LC-expressing cell lines were generated and transplanted into mice. A lambda6 LC gene was cloned from a patient with aggressive multi-organ AL amyloidosis and stably expressed in SP2/0 plasmacytoma cells, which were injected into syngeneic Balb/c and RAG-/- mice. Four to six weeks later, echocardiograms were performed and the mice were euthanized and serum, urine, and tissues were collected. Mice injected with LC-producing cells had detectable circulating human LC in their serum and some mice excreted LC and albumin in the urine, whereas mice injected with untransfected cells did not. In the kidney, there were amorphous protein deposits and early glomerulopathy by electron microscopy in two mice examined, but no mature fibril deposition. These mice had bradycardia and upregulation of the cell stress marker heme oxygenase-1 in the heart. Therefore, short-term expression of human amyloidogenic LC in mice in vivo produces alterations in kidney and heart function prior to the development of fibrillar deposits. However, the tumor model is unsuitable for long-term studies because of overgrowth of the plasmacytoma cells. To circumvent this problem, a transgenic model was developed in which the same lambda6 LC gene was expressed using a CMV promoter. In three transgenic lines, LC is expressed in epithelial cells and found in serum and urine. Thus, these mice will be useful for the study of accessory factors in amyloidogenesis and for the development of novel therapeutic approaches.
590 $a School code: 0017.
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Biology, Microbiology. $3 1017734
650 4 $a Health Sciences, Immunology. $3 1017716
690 $a 0307
690 $a 0410
690 $a 0982
710 2 0 $a Boston University. $3 1017454
773 0 $t Dissertation Abstracts International $g 66-11B.
790 1 0 $a Seldin, David C., $e advisor
790 $a 0017
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3194777