Transgenic Mice Expressing Human ApoB95 and ApoB97

Bibliographic Details
Title:	Transgenic Mice Expressing Human ApoB95 and ApoB97
Authors:	McCormick, Sally P.A., Ng, Jennifer K., Cham, Candace M., Taylor, Stacy, Marcovina, Santica M., Segrest, Jere P., Hammer, Robert E., Young, Stephen G.
Source:	Journal of Biological Chemistry; September 1997, Vol. 272 Issue: 38 p23616-23622, 7p
Abstract:	The structural features of apolipoprotein (apo) B that are important for its covalent linkage to apo(a) to form lipoprotein(a) (Lp(a)) are incompletely understood. Although apoB100 cysteine 4326 is required for the disulfide linkage with apo(a), other structural features, aside from a single free cysteine residue, must be important for apoB's initial interaction with apo(a) and for facilitating the formation of the disulfide bond. To determine if sequences carboxyl-terminal to cysteine 4326 affect the efficiency of Lp(a) formation, we used “pop-in, pop-out” gene targeting in a human apoB yeast artificial chromosome to introduce nonsense mutations into exon 29 of the apoB gene. The mutant yeast artificial chromosomes, which coded for the truncated versions of human apoB, apoB95, and apoB97, were then used to express these mutant forms of apoB in transgenic mice. As judged by in vitroassays of Lp(a) formation, apoB95 (4330 amino acids) formed a small amount of Lp(a) but did so slowly. In contrast, apoB97 (4397 amino acids) formed Lp(a) rapidly, although not quite as rapidly as the full-length apoB100 (4536 amino acids). These results were supported by an analysis of double-transgenic mice expressing both human apo(a) and either apoB95 or apoB97. In mice expressing both apoB95 and apo(a), there was only a trace amount of Lp(a) in the plasma, and most of the apo(a) was free, whereas in mice expressing both apoB97 and apo(a), virtually all of the apo(a) was bound to apoB97 in the form of Lp(a). These results show that sequences carboxyl-terminal to apoB95 (amino acids 4331–4536) are not absolutely required for Lp(a) formation, but this segment of the apoB molecule, particularly residues 4331–4397, is necessary for the efficient assembly of Lp(a).
Database:	Supplemental Index

FullText	Links: – Type: other Text: Availability: 0 CustomLinks: – Url: https://www.doi.org/10.1074/jbc.272.38.23616? Name: ScienceDirect (all content)-s8985755 Category: fullText Text: View record from ScienceDirect MouseOverText: View record from ScienceDirect – Url: https://resolver.ebsco.com/c/xy5jbn/result?sid=EBSCO:edo&genre=article&issn=00219258&ISBN=&volume=272&issue=38&date=19970919&spage=23616&pages=23616-23622&title=Journal of Biological Chemistry&atitle=Transgenic%20Mice%20Expressing%20Human%20ApoB95%20and%20ApoB97&aulast=McCormick%2C%20Sally%20P.A.&id=DOI:10.1074/jbc.272.38.23616 Name: Full Text Finder (for New FTF UI) (s8985755) Category: fullText Text: Find It @ SCU Libraries MouseOverText: Find It @ SCU Libraries
Header	DbId: edo DbLabel: Supplemental Index An: ejs55931302 RelevancyScore: 804 AccessLevel: 6 PubType: Periodical PubTypeId: serialPeriodical PreciseRelevancyScore: 803.93701171875
IllustrationInfo
Items	– Name: Title Label: Title Group: Ti Data: Transgenic Mice Expressing Human ApoB95 and ApoB97 – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22McCormick%2C+Sally+P%2EA%2E%22">McCormick, Sally P.A.</searchLink><br /><searchLink fieldCode="AR" term="%22Ng%2C+Jennifer+K%2E%22">Ng, Jennifer K.</searchLink><br /><searchLink fieldCode="AR" term="%22Cham%2C+Candace+M%2E%22">Cham, Candace M.</searchLink><br /><searchLink fieldCode="AR" term="%22Taylor%2C+Stacy%22">Taylor, Stacy</searchLink><br /><searchLink fieldCode="AR" term="%22Marcovina%2C+Santica+M%2E%22">Marcovina, Santica M.</searchLink><br /><searchLink fieldCode="AR" term="%22Segrest%2C+Jere+P%2E%22">Segrest, Jere P.</searchLink><br /><searchLink fieldCode="AR" term="%22Hammer%2C+Robert+E%2E%22">Hammer, Robert E.</searchLink><br /><searchLink fieldCode="AR" term="%22Young%2C+Stephen+G%2E%22">Young, Stephen G.</searchLink> – Name: TitleSource Label: Source Group: Src Data: Journal of Biological Chemistry; September 1997, Vol. 272 Issue: 38 p23616-23622, 7p – Name: Abstract Label: Abstract Group: Ab Data: The structural features of apolipoprotein (apo) B that are important for its covalent linkage to apo(a) to form lipoprotein(a) (Lp(a)) are incompletely understood. Although apoB100 cysteine 4326 is required for the disulfide linkage with apo(a), other structural features, aside from a single free cysteine residue, must be important for apoB's initial interaction with apo(a) and for facilitating the formation of the disulfide bond. To determine if sequences carboxyl-terminal to cysteine 4326 affect the efficiency of Lp(a) formation, we used “pop-in, pop-out” gene targeting in a human apoB yeast artificial chromosome to introduce nonsense mutations into exon 29 of the apoB gene. The mutant yeast artificial chromosomes, which coded for the truncated versions of human apoB, apoB95, and apoB97, were then used to express these mutant forms of apoB in transgenic mice. As judged by in vitroassays of Lp(a) formation, apoB95 (4330 amino acids) formed a small amount of Lp(a) but did so slowly. In contrast, apoB97 (4397 amino acids) formed Lp(a) rapidly, although not quite as rapidly as the full-length apoB100 (4536 amino acids). These results were supported by an analysis of double-transgenic mice expressing both human apo(a) and either apoB95 or apoB97. In mice expressing both apoB95 and apo(a), there was only a trace amount of Lp(a) in the plasma, and most of the apo(a) was free, whereas in mice expressing both apoB97 and apo(a), virtually all of the apo(a) was bound to apoB97 in the form of Lp(a). These results show that sequences carboxyl-terminal to apoB95 (amino acids 4331–4536) are not absolutely required for Lp(a) formation, but this segment of the apoB molecule, particularly residues 4331–4397, is necessary for the efficient assembly of Lp(a).
PLink	https://login.libproxy.scu.edu/login?url=https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edo&AN=ejs55931302
RecordInfo	BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1074/jbc.272.38.23616 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 7 StartPage: 23616 Titles: – TitleFull: Transgenic Mice Expressing Human ApoB95 and ApoB97 Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: McCormick, Sally P.A. – PersonEntity: Name: NameFull: Ng, Jennifer K. – PersonEntity: Name: NameFull: Cham, Candace M. – PersonEntity: Name: NameFull: Taylor, Stacy – PersonEntity: Name: NameFull: Marcovina, Santica M. – PersonEntity: Name: NameFull: Segrest, Jere P. – PersonEntity: Name: NameFull: Hammer, Robert E. – PersonEntity: Name: NameFull: Young, Stephen G. IsPartOfRelationships: – BibEntity: Dates: – D: 19 M: 09 Text: September 1997 Type: published Y: 1997 Identifiers: – Type: issn-print Value: 00219258 – Type: issn-print Value: 1083351X Numbering: – Type: volume Value: 272 – Type: issue Value: 38 Titles: – TitleFull: Journal of Biological Chemistry Type: main
ResultId	1