• Lp(a) gene encoding apo(a), bound to apoB-100 by noncovalently and covalently way to assembly of the Lp(a) particles. Lp(a) particles are highly polymorphic particles that are structurally similar to but larger than low-density lipoprotein (LDL).  Apo(a) has multiple repeated copies of sequences homologous to plasminogen's kringle 4 domain (KIV), followed by a kringle 5-like (KV) domain and a protease-like domain. Therein, KIV2 multiple copies determine apo(a) isoform size, which is inversely correlated with plasma levels. The Lp(a) concentration is heterogeneous and, to a major extent, controlled by genetics. Other factors such as ethnicity and race, medical and environmental conditions also play roles in Lp(a) regulation. Lp(a) has been associated with increased risks of atherosclerosis, thrombosis, and aortic valve calcification.
• Biocytogen developed an LPA humanized mice, the full coding sequences of human LPA gene that driven by the Alb promoter was inserted into the Gt(ROSA)26Sor gene locus site.
• PCSK9 is expressed in liver, intestine and kidney tissues and escorts specific receptors for lysosomal degradation. It plays a role in cholesterol and fatty acid metabolism. PCSK9 binds to the receptor for LDL if PCSK9 is blocked, more LDLRs are recycled and are present on the surface of cells to remove LDL-particles from the extracellular fluid.
• Biocytogen developed an PCSK9 humanized mice. The genome of the mouse Pcsk9 gene including 5’UTR and 3’UTR was replaced by human PCSK9 genome including 5’UTR and 3’UTR in B-hPCSK9 mice plus.
• APOB is the main apolipoprotein of chylomicrons and low density lipoproteins. It occurs in plasma as two main isoforms, apoB-48 and apoB-100, which encoded by a single gene APOB, the shorter apoB-48 protein is produced after RNA editing of the apoB-100 transcript at residue 2180 (CAA->UAA) and early translation termination. Apob-48 is is synthesized in gut and apoB-100 in liver.
• Biocytogen developed an APOB humanized mice. The exons 1-29 of mouse Apob gene that encode the whole molecule (ATG to STOP codon), including 5’UTR and 3’UTR were replaced by human counterparts in B-hAPOB mice. The human APOB expression is driven by human APOB promoter, while mouse Apob gene transcription and translation will be disrupted.
• B-hLPA/hAPOB/hPCSK9 plus mice were derived from mating B-hLPA mice (112723), B-hAPOB mice (112951) and hPCSK9 mice plus (112751). For validation data of this mouse model, you can refer to the validation data from the related gene humanized mouse models.

• B-hLPA/hAPOB/hPCSK9 plus mice were derived from mating B-hLPA mice (112723), B-hAPOB mice (112951), and hPCSK9 mice plus (112751). For validation data of this mouse model, you can refer to the validation data from the related gene humanized mouse models.
• Gene targeting strategy for B-hLPA mice. The full coding sequences of the human LPA gene, which was driven by Alb promoter was inserted into the Gt(ROSA)26Sor gene locus site. And there’s no LPA gene in the mouse genome sequence.
• Gene targeting strategy for B-hAPOB mice. The exons 1-29 of the mouse Apob gene that encode the whole molecule (ATG to STOP codon), including 5’UTR and 3’UTR, were replaced by human counterparts in B-hAPOB mice. The human APOB expression is driven by the human APOB promoter, while mouse Apob gene transcription and translation will be disrupted.
• Gene targeting strategy for B-hPCSK9 mice plus. The genome of the mouse Pcsk9 gene, including 5’UTR and 3’UTR, was replaced by human PCSK9 genome, including 5’UTR and 3’UTR, in B-hPCSK9 mice plus. The human PCSK9 expression is driven by human PCSK9 promoter, while mouse Pcsk9 gene transcription and translation will be disrupted.

Strain specific PCSK9 expression analysis in homozygous humanized B-hLPA/hAPOB/hPCSK9 plus mice by ELISA. Serum was collected from homozygous B-hLPA/hAPOB/hPCSK9 plus mice (H/H, H/H, H/H) (6 weeks old, male, n=3; female, n=3). Protein expression level of PCSK9 was analyzed by ELISA (Human PCSK9 ELISA Kit, Proteintech, KE00278). Values are expressed as mean ± SEM.

Strain specific Apo(a) protein analysis in homozygous humanized B-hLPA/hAPOB/hPCSK9 plus mice by ELISA. Serum was collected from homozygous B-hLPA/hAPOB/hPCSK9 plus mice (H/H, H/H, H/H) (6 weeks old, male, n=5; female, n=3). Protein expression level of Apo(a) was analyzed by ELISA (Human Lipoprotein A ELISA Kit, Abcam, ab212165). Values are expressed as mean ± SEM.