• 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) have 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. There in, 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 calcification1,2. 
• Biocytogen developed another novel LPA humanized mice (B-hLPA mice plus), the BAC contains human Lpa gene promoter and the full coding region genome sequences (include intron) as well as UTR was inserted into the Gt(ROSA)26Sor gene locus site. Then, confirmed that human Apo(a) protein was detected in the serum of heterozygous B-hLPA mice plus. 
• The mice can be used for preclinical pharmacodynamics studies of target-related disease.

Species-specific analysis of LPA gene expression in heterozygous B-hLPA mice plus by RT-qPCR. Liver tissues were collected from wild-type C57BL/6JNifdc mice (+/+) and heterozygous B-hLPA mice plus (H/+) (3 males and 3 females, 8 weeks old), then cDNA libraries were synthesized by reverse transcription, followed by qPCR with human LPA primers. 

Strain-specific Apo(a) protein expression analysis in B-hLPA mice plus by ELISA. Serum were collected from homozygous B-hLPA mice plus (H/H), (n=3, 6 weeks old). Expression level of human Apo(a) was analyzed by ELISA (Abcam, ab212165). Human Apo(a) was detectable in homozygous B-hLPA mice plus, and human Apo(a) expression levels were higher in females than males in B-hLPA mice plus.

Strain-specific Apo(a) protein expression analysis in B-hLPA mice plus by ELISA. Serum were collected from heterozygous B-hLPA mice plus (H/H), (n=3, 9-17 weeks old). Expression level of human Apo(a) was analyzed by ELISA (Abcam, ab212165). Human Apo(a) was detectable in heterozygous B-hLPA mice plus, and human Apo(a) expression levels were higher in females than males in B-hLPA mice plus. The expression of human Apo(a) in male B-hLPA mice plus decreased as the weeks of age increase.

Changes of Apo(a) levels in heterozygous B-hLPA mice plus in response to olpasiran-analog. Olpasiran analog (provided by the client) is a double-stranded small interfering RNA (siRNA) targeting lipoprotein(a). (A) The schematic diagram of experimental processing.  (B) The expression of human Apo(a) in serum of heterozygous B-hLPA mice plus (H/+).

Note: The expression of human Apo(a) in male B-hLPA mice plus decreased as the weeks of age increase.