The enzyme phospholipase D (PLD) and its activator ADP ribosylation factor 6 (ARF6) have been found to be involved in the pathogenesis and progression of a variety of diseases, including Alzheimer’s Disease (AD) and various cancers. As such, the two isoforms of phospholipase D found in human cells, PLD1 and PLD2, and ARF6 are promising potential drug targets for AD therapeutics. This technology describes several lines of genetically modified mice with mutant Pld1, Pld2, or Arf6 alleles that can be used to breed mouse models for AD drug development research, as well as for studying other diseases associated with dysregulation of these pathways.
Several of the mouse strains described in this technology leverage Cre-LoxP recombination to enable precise control over knockdown of Pld1, Pld2, or Arf6. Here, LoxP gene sequences have been inserted into the mouse genome to flank the genes of interest. When bred with other transgenic mice that express Cre recombinase, the mice described here can be used to generate offspring with selectively ablated Pld1, Pld2, or Arf6. This system allows control over expression of the genes of interest in a cell-, tissue-, and/or time-dependent manner. Additionally, knockout mice entirely lacking one or both functional copies of the Pld1 or Pld2 gene have also been generated. Given the central roles Pld1, Pld2, and Arf6 play in cell regulation and signaling, these mouse models may be useful for mechanistic or drug development research on neurodegenerative diseases, lipid metabolism disorders, cardiovascular disease, liver disease, diabetes, and cancer.
These mouse models have been used in published studies evaluating the mechanistic roles of Pld1 and Pld2 in AD pathogenesis.
Tech Ventures Reference: IR CU16275, IR CU16276, IR CU16277, IR CU16278, IR CU16279