These transgenic mice express a human <i>ATXN3</i>, ataxin 3, gene (a cDNA fragment encoding amino acid 286 to the C terminus, with 77 polyglutamine repeats, obtained from a patient with Machado-Joseph disease), under the control of the human <i>HCRT</i>, hypocretin (orexin) neuropeptide precursor, 3.2 kb upstream region, promoter.  In transgenic mice, approximately 12 weeks of age, transgene expression results in the ablation of hypocretin (orexin) neurons (&gt;99% loss).  By 2 weeks of age, transgenic mice exhibit a loss of approximately half of hypocretin (orexin) containing neurons.  Transgenic mice display reduced stress-induced hyperthermia, hypoactivity, and lower basal arterial blood pressure than wildtype controls.  At approximately 6 weeks of age, transgenic mice display narcoleptic episodes consisting of a sudden stop to motor activity, postural changes, and ending with complete resumption of motor activity.
While transgenic mice exhibit a level of sensitivity to anesthesia (induction of anesthesia) that is similar to wildtype controls, mutant mice have a delayed emergence from anesthesia (50% more time to emerge for both isoflurane and sevoflurane).  No cataplectic episodes were detected during anesthesia experiments.  Transgenic mice exhibit shorter retention of social recognition when compared to wildtype controls.  Hippocampal synaptic plasticity is altered with both paired pulse facilitation (PPF) and long-term potentiation (LTP) are attenuated.  Mice that are hemizygous for the targeted mutation are viable and fertile.  The Donating Investigator has not attempted to make the strain homozygous.



Hypocretin (orexin) containing neurons are ablated in these transgenic mice, which may be useful in studies of narcolepsy, regulation of sleep/wakefulness, feeding behavior, and metabolic homeostasis.

Typically mice are recovered in 12-16 weeks. Contact Customer Service to place an order or for more information.

<a target="_blank" href="https://www.jax.org/jax-mice-and-services/customer-support" rel="noreferrer">Contact Customer Service</a> for more information.