Apolipoprotein(a) yeast artificial chromosome transgenic rabbits. Lipoprotein(a) assembly with human and rabbit apolipoprotein B.
The in vivo analysis of lipoprotein(a) (Lp(a)), an independent atherosclerosis risk factor in humans, has been limited in part by its restricted distribution among mammals. Although transgenic mice have been created containing Lp(a), the relatively small size of the mouse has precluded some studies. To examine the properties of this molecule in a significantly larger mammal, we have used a 270-kilobase yeast artificial chromosome clone containing the human apolipoprotein(a) (apo(a)) gene and a 90-kilobase P1 phagemid clone containing the human apolipoprotein B (apoB) gene to create transgenic rabbits that express either or both transgenes. Expression of both transgenes was tissue specific and localized predominantly to the liver. Average apolipoprotein plasma levels in the rabbits were 2.5 mg/dl for apo(a) and 17.6 mg/dl for human apoB. In contrast to observations in apo(a) transgenic mice, we found that apo(a) plasma levels in the rabbits were stable throughout sexual maturity. Also, apo(a) formed a covalent association with the endogenous rabbit apoB albeit with a lower efficiency than its association with human apoB. The analysis of Lp(a) transgenic rabbits has provided new insights into apo(a) expression and Lp(a) assembly. In addition, these transgenic rabbits potentially will provide an improved experimental model for the in vivo analysis of Lp(a) and its role in promoting atherosclerosis and restenosis.
Rouy
D
D
Rhône-Poulenc Rorer-Gencell, Atherosclerosis Department, Centre de Recherche de Vitry-Alfortville, 94403 Vitry sur Seine Cedex, France.
Duverger
N
N
Lin
S D
SD
Emmanuel
F
F
Houdebine
L M
LM
Denefle
P
P
Viglietta
C
C
Gong
E
E
Rubin
E M
EM
Hughes
S D
SD
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001053:Apolipoproteins / Q000235:genetics* / Q000378:metabolism; D053241:Apoprotein(a); D001665:Binding Sites; D018244:Chromosomes, Artificial, Yeast; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017270:Lipoprotein(a); D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D011555:Pseudopregnancy; D011817:Rabbits; D017386:Sequence Homology, Amino Acid
D001053:Apolipoproteins; D017270:Lipoprotein(a); D053241:Apoprotein(a)