Lipoprotein(a) (Lp(a)) is a lipoprotein particle consisting of apolipoprotein(a) (Apo(a)) bound to low-density lipoprotein (LDL) containing apolipoprotein B (ApoB), where the LPA gene encoding for Apo(a) is only found in the genomes of humans and some non-human primates. LP(a) is similar in size and lipid content to low-density lipoprotein (LDL) and is considered a new risk factor for several cardiovascular diseases (CVD), including atherosclerosis, coronary heart disease, and stroke ^[1]. Lp(a) differs from LDL in that it contains an additional variable-length Apo(a), which covalently binds to ApoB-100 via a single disulfide bond. Lp(a) plays a crucial role in systemic lipid transport, guiding inflammatory cells into blood vessel walls and promoting smooth muscle cell proliferation. Additionally, it participates in wound healing and tissue repair, interacting with components of the blood vessel wall and extracellular matrix ^[2]. However, Lp(a) can also cause arterial narrowing by adhering to the arterial wall, accelerating blood clot formation, and triggering pathological changes related to coronary heart disease, atherosclerosis, thrombosis, and stroke ^[3]. The plasma concentration of Lp(a) is closely related to genetic factors, primarily regulated by the LPA gene. Consequently, the LPA gene represents an important potential target for cardiovascular disease treatment. Currently, several novel therapies aimed at modulating LPA gene transcription rates are under development, including small interfering RNA (siRNA) and antisense oligonucleotide (ASO) drugs ^[4]. Given that the LPA gene is expressed only in humans and some non-human primates but not in mice, constructing a mouse model expressing the human LPA gene is crucial for the preclinical evaluation of lipid-lowering drugs.

The H11-Alb-hLPA mouse is a humanized model where the human LPA protein coding sequence (CDS) is integrated into the mouse H11 safe harbor locus. In this model, the human LPA gene is specifically expressed in the liver under the control of the mouse Alb promoter. It can be used to study the pathogenic mechanisms of the LPA gene in hyperlipidemia and related cardiovascular diseases, as well as to evaluate targeted drug development. Additionally, Cyagen has developed a conditionally inducible LPA humanization model (catalog number: C001521) using the CAG promoter. When crossed with Alb-Cre mice (liver-specific Cre mice), the resulting LPA-humanized mice (catalog number: C001522) exhibit significantly higher LPA protein levels compared to the H11-Alb-hLPA mice. Therefore, researchers please choose the appropriate mouse strain based on their specific requirements for LPA protein expression levels and genetic characteristics.