Lmf2-KO Mouse

Lmf2, or Lipase maturation factor 2, is a member of the LMF family proteins. These proteins are essential for the maturation and transport of active lipoprotein lipases, suggesting Lmf2 plays a role in lipid metabolism pathways [2].

In Alzheimer's disease (AD) and amnesic mild cognitive impairment (aMCI), DNA methylation levels in the NCAPH2/LMF2 promoter region are significantly decreased compared to normal controls, potentially serving as a biomarker for diagnosis [3]. Moreover, this methylation is associated with hippocampal atrophy in AD and aMCI patients, possibly through apoptosis [1]. In the grain aphid, silencing of a lmf2-like gene by wheat-mediated RNAi reduces the aphid's survivability and reproductive capacity, indicating its importance in aphid growth and reproduction [2]. Also, a burden of rare predicted loss-of-function (pLOF) variants in Lmf2 is associated with increased hepatic fat [4]. In sheep, Lmf2 is involved in fast metabolism, and its associated copy number variations (CNVs) are associated with climatic variables, suggesting a role in climate-related adaptation [5].

In summary, Lmf2 is crucial for lipoprotein lipase maturation and has implications in multiple biological processes and disease conditions. Its role in lipid metabolism, as well as its associations with AD, aMCI, aphid survival, hepatic fat, and sheep metabolism adaptation, underscores its significance. The study of Lmf2 using genetic models like RNAi in aphids and identification of genetic variants in humans and sheep, helps in understanding its functions and disease associations.

References:

1. Shinagawa, Shunichiro, Kobayashi, Nobuyuki, Nagata, Tomoyuki, Kondo, Kazuhiro, Nakayama, Kazuhiko. 2016. DNA methylation in the NCAPH2/LMF2 promoter region is associated with hippocampal atrophy in Alzheimer's disease and amnesic mild cognitive impairment patients. In Neuroscience letters, 629, 33-37. doi:10.1016/j.neulet.2016.06.055. https://pubmed.ncbi.nlm.nih.gov/27356276/

2. Xu, Lanjie, Hou, Qiling, Zhao, Yanjie, Ni, Zhongfu, Liang, Rongqi. 2017. Silencing of a lipase maturation factor 2-like gene by wheat-mediated RNAi reduces the survivability and reproductive capacity of the grain aphid, Sitobion avenae. In Archives of insect biochemistry and physiology, 95, . doi:10.1002/arch.21392. https://pubmed.ncbi.nlm.nih.gov/28618004/

3. Kobayashi, Nobuyuki, Shinagawa, Shunichiro, Nagata, Tomoyuki, Nakayama, Kazuhiko, Kondo, Kazuhiro. 2016. Development of Biomarkers Based on DNA Methylation in the NCAPH2/LMF2 Promoter Region for Diagnosis of Alzheimer's Disease and Amnesic Mild Cognitive Impairment. In PloS one, 11, e0146449. doi:10.1371/journal.pone.0146449. https://pubmed.ncbi.nlm.nih.gov/26742120/

4. Park, Joseph, MacLean, Matthew T, Lucas, Anastasia M, Witschey, Walter R, Rader, Daniel J. 2022. Exome-wide association analysis of CT imaging-derived hepatic fat in a medical biobank. In Cell reports. Medicine, 3, 100855. doi:10.1016/j.xcrm.2022.100855. https://pubmed.ncbi.nlm.nih.gov/36513072/

5. Salehian-Dehkordi, Hosein, Huang, Jia-Hui, Pirany, Nasrollah, Esmailizadeh, Ali, Lv, Feng-Hua. 2023. Genomic Landscape of Copy Number Variations and Their Associations with Climatic Variables in the World's Sheep. In Genes, 14, . doi:10.3390/genes14061256. https://pubmed.ncbi.nlm.nih.gov/37372436/