Lrpap1-KO Mouse

Lrpap1, also known as receptor associated protein (RAP), is an endoplasmic reticulum chaperone and inhibitor of LDL receptor related protein 1 (LRP1) and related receptors. It is involved in ensuring proper formation of intermolecular disulfide bonds during LDL receptor biogenesis and escorts receptors through the endoplasmic reticulum and early Golgi compartment to prevent premature ligand-receptor interaction [4]. It has been associated with various biological processes and diseases, playing a role in lipid metabolism, immune response, and more. Genetic models such as knockout models can be valuable for further understanding its functions.

In zebrafish, lrpap1 deficiency leads to myopia through TGF-β-induced apoptosis. Homozygous mutant zebrafish showed myopic phenotypes with changes in eye axial length, scleral collagen fiber structure, and activation of apoptosis signaling [1]. In mouse microglial cell lines, activated or stressed microglia release LRPAP1, which can inhibit microglial phagocytosis and amyloid beta aggregation [2]. In humans, frameshift mutations in LRPAP1 are responsible for autosomal recessive high myopia, and childhood myopic foveoschisis can develop in those with LRPAP1-associated myopia [1,3].

In conclusion, Lrpap1 is crucial for multiple biological processes. Its deficiency in zebrafish models reveals its role in ocular refractive development and myopia. In microglial cell models, its release and function in regulating microglial activities and amyloid-beta pathology are demonstrated. These model-based studies contribute to understanding diseases related to myopia and neurodegeneration associated with amyloid-beta aggregation.

References:

1. Liu, Shanshan, Chen, Ting, Chen, Binghao, Lu, Xiaohe, Li, Jiali. 2022. Lrpap1 deficiency leads to myopia through TGF-β-induced apoptosis in zebrafish. In Cell communication and signaling : CCS, 20, 162. doi:10.1186/s12964-022-00970-9. https://pubmed.ncbi.nlm.nih.gov/36261846/

2. Reid, Kyle M, Brown, Guy C. 2023. LRPAP1 is released from activated microglia and inhibits microglial phagocytosis and amyloid beta aggregation. In Frontiers in immunology, 14, 1286474. doi:10.3389/fimmu.2023.1286474. https://pubmed.ncbi.nlm.nih.gov/38035103/

3. Almazyead, Mohammad, Alfakhri, Abdullmajeed S, Alsulaiman, Sulaiman M. 2024. Childhood Myopic Foveoschisis in LRPAP1-associated Myopia. In Middle East African journal of ophthalmology, 30, 182-184. doi:10.4103/meajo.meajo_151_23. https://pubmed.ncbi.nlm.nih.gov/39444998/

4. Neuhaus, Herbert, Gaul, Florian, Hollemann, Thomas. . lrpap1 as a specific marker of proximal pronephric kidney tubuli in Xenopus laevis embryos. In The International journal of developmental biology, 62, 319-324. doi:10.1387/ijdb.170295hn. https://pubmed.ncbi.nlm.nih.gov/29877571/