Lamc3-KO Mouse

Lamc3, encoding laminin γ3 chain, is crucial for structural support and cellular processes. It functions mainly through protein-containing complex binding and signaling receptor binding, and is associated with pathways like extracellular matrix receptor interaction and PI3K-Akt signaling pathway [1]. The proteins encoded by genes interacting with Lamc3 are mainly located in the basement membrane and extracellular matrix component [1].

Recessive or complex heterozygous variants of the Lamc3 gene cause occipital cortical malformation (OCCM), characterized by polymicrogyria and pachygyria of the occipital lobes and childhood-onset seizures [1]. Functional experiments have confirmed that certain variant sites lead to premature truncation of the laminin γ3 chain [1]. In ovarian cancer, low expression of LAMC3 is related to poor prognosis and malignant progression, potentially through regulating oncogene-pathways like Rap1, MAPK, Ras and cell adhesion-related pathways such as ECM-receptor interaction and focal adhesion [2]. Also, a novel homozygous frameshift variant in Lamc3 in the Finnish population causes severe epilepsy and cortical malformations, with variable epilepsy phenotypes [3].

In conclusion, Lamc3 plays a vital role in maintaining normal brain development and function, as well as in the prognosis of ovarian cancer. Research on Lamc3 variants, especially in the context of genetic models, helps to understand its role in these biological processes and disease conditions, providing insights for potential therapeutic strategies.

References:

1. Qian, Xiaohang, Liu, Xiaoying, Zhu, Zeyu, Tang, Huidong, Cao, Li. 2021. Variants in LAMC3 Causes Occipital Cortical Malformation. In Frontiers in genetics, 12, 616761. doi:10.3389/fgene.2021.616761. https://pubmed.ncbi.nlm.nih.gov/34354730/

2. Lei, S M, Liu, X, Xia, L P, Li, L, Yin, F J. . [Relationships between decreased LAMC3 and poor prognosis in ovarian cancer]. In Zhonghua fu chan ke za zhi, 56, 489-497. doi:10.3760/cma.j.cn112141-20210426-00230. https://pubmed.ncbi.nlm.nih.gov/34304441/

3. Saarela, Anni, Timonen, Oskari, Kirjavainen, Jarkko, Mervaala, Esa, Kälviäinen, Reetta. 2024. Novel LAMC3 pathogenic variant enriched in Finnish population causes malformations of cortical development and severe epilepsy. In Epileptic disorders : international epilepsy journal with videotape, 26, 498-509. doi:10.1002/epd2.20244. https://pubmed.ncbi.nlm.nih.gov/38758065/