Isolation and genetic characterization of the porcine apolipoprotein E gene

Abstract

The present report describes the isolation and genetic characterization of the porcine apolipoprotein E (apo-E) gene. A single positive recombinant phage clone containing a 10.7-kb insert was isolated from a porcine genomic library, and a 4.2-kb fragment was subcloned and sequenced. The 4.2-kb fragment contained the entire apo-E gene in addition to upstream and downstream sequences (GenBank accession no. 470240). The porcine apo-E gene is made up of four exons and three introns, and encodes a preapo-E protein comprised of a signal peptide of 18 amino acids and a mature protein of 299 amino acids. The porcine apo-E gene contains a (CG)13 microsatellite marker within intron three. This microsatellite is moderately polymorphic, and at least four alleles were evident at this locus among 10 animals from each of the Yorkshire, Hampshire, Landrace and Duroc breeds. Finally, localization of the porcine apo-E gene to chromosome 6 band q2.1 was determined by fluorescent in situ hybridization and confirmed by genetic linkage analysis.

A genetically modified minipig model for Alzheimer’s disease with SORL1 haploinsufficiency

“… 32 Of special relevance for modeling AD, human and pig APP sequences have very high similarity, sharing identical secretase cleavage sites for production of Aβ fragments found in humans. 33 The APOE allele status of pigs in general (including Göttingen minipigs; C.B.S., unpublished data) has been reported as APOE-e4 ; 34 , 35 thus, they may have an inherent genetic disposition for developing AD in analogy to humans, in which this isoform is associated with high risk of the disease. Importantly, the pig has a body size and longevity enabling deployment of CSF and neuroimaging markers used in the clinical setting of AD diagnosis and allowing longitudinal monitoring of these, as the lifespan can reach as high as 15 years.…”

Primary Genetic Investigation of a Hyperlipidemia Model: Molecular Characteristics and Variants of the Apolipoprotein E Gene in Mongolian Gerbil

“…There is no age or sex difference in the distribution of genotype frequencies but there are differences in genotype frequency among diverse ethnicities [39]. There are few reports of SNPs in rat and mouse and only 7 of SNPs in pig [24]. SNPs within the promoter region exert a marked influence on transcription of the porcine ApoE gene [40].…”

Apolipoprotein E Deficiency Increases Remnant Lipoproteins and Accelerates Progressive Atherosclerosis, But Not Xanthoma Formation, in Gene-Modified Minipigs

“…As human APOE , the porcine APOE gene consists of 4 exons and the porcine protein has an amino acid similarity of 70.3% compared to human APOE 11 , 12 . The recombinant adeno-associated virus (rAAV)/ APOE knockout (KO) vector was constructed as previously described 13 , 14 .…”