Columbia University

Technology Ventures

Transgenic mouse strain allows inducible genetic expression in kidney cells and nervous system

Technology #cu14313

Mouse models play an important role in the study of diseases. The Cre-LoxP recombination system has become a useful tool in controlling genetic expression in transgenic mice and permits the manipulation of genes in individual organs or cells to mimic mutations in human diseases. This technology is a mouse strain containing a tamoxifen-dependent Cre recombinase (CreERT2) driven by the glial cell line-derived neurotrophic factor (GDNF) promoter, which can be used to drive Cre-LoxP recombination in kidney cells and parts of the central and enteric nervous system. Cell death or modifications can be induced using tamoxifen at various time points in the developing mouse kidney to observe for whole system consequences in adult mice. Thus, this technology has potential to contribute towards mice model research in kidney or nervous system diseases.

Rescue by endogenous gene preserves normal development in transgenic mice

While there are benefits to the Cre-LoxP recombination system, it requires the insertion of the Cre gene into the mouse genome, and the disruption of the insertion to the endogenous gene sometimes has adverse effects on the mouse. Mice require GDNF for kidney development, and mice with one or both copies of the GDNF gene knocked out exhibit renal disorders as well as lack of most the enteric nervous system. This technology bypasses this problem by co-inserting the GDNF cDNA sequence at the endogenous GDNF locus along with the CreERT2 gene. The inserted GDNF cDNA is sufficient to rescue renal disorders and allow the transgenic mice to develop normally without hindering the use of the Cre-Lox system in specifically the kidneys and the nervous system.

Expression of the GDNF-CreERT2 were first assessed in the transgenic mice using a fluorescent reporter in vitro and in vivo. The efficacy of the tamoxifen-induced Cre-LoxP recombinant mice was then tested by inducing cell death in a fraction of the kidney cells. It was verified that both heterozygous and homozygous mice with this transgene developed normally into adulthood.

Lead Inventor:

Frank Costantini, Ph.D.

Applications:

  • Strain of transgenic mice to conduct experiments involving inducible cellular modifications in kidney cells and/or the nervous system
  • Potential enhancement of GDNF in the endogenous GDNF-producing cells for therapeutic research for Parkinson’s disease
  • Further research into how low nephron numbers affect hypertension

Advantages:

  • Provides ability to induce genetic modification in the kidney or nervous system at any time in the mouse development
  • Transgenic mice develop normally without disorders associated with disruptions in the endogenous gene
  • Provides cellular modification in parts of the nervous system that previous mice lines may not allow

Patent information:

Patent Pending

Tech Ventures Reference: IR CU14313

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