Neuroscience Portfolio

Humanized Apolipoprotein E (APOE) mice

The Apoe gene is the strongest genetic risk factor for sporadic forms of late-onset Alzheimer Disease (AD). Taconic provides three humanized APOE mouse models that are useful for studying the role of human APOE polymorphism neurodegenerative disorders.

The association of specific APOE isoform expression with human neurodegenerative disorders has focused attention on the role of these APOE isoforms in lipoprotein receptor-dependent synaptic modulation. Targeting APOE and APOE receptor pathways represents promising therapeutic strategies to combat neurodegenerative diseases such as Alzheimer’s Disease.

APOE is a plasma protein involved in cholesterol transport with three human isoforms (E2, E3, and E4). Among the three isoforms APOE4 appears to drive amyloid pathology by inhibiting brain clearance of amyloid-β (Aβ) peptides and by promoting Aβ aggregation.

In the brain, APOE is primarily synthesized by astrocytes and microglia and is lipidated by the ABCA1 transporter to form lipoprotein particles. Lipidated APOE binds to soluble Aβ and facilitates Aβ uptake through cell surface receptors

Taconic offers several models (sponsored by The Michael J Fox Foundation) for the study of Parkinson's Disease.

Cryopreserved models

Copy number variations (CNVs) are a type of genetic structural variation involving deletions or duplications of specific and relatively large (>1 kb) regions of DNA. Geneticists now recognize that CNVs and other rare structural variants contribute to the genetic basis of common diseases and disorders, including autism and schizophrenia.

Taconic offers neuropsychiatric disorder CNV models that develop distinct neurological and behavioral phenotypes. These models can be used to screen novel drug candidates for treating schizophrenia, autism spectrum disorders, epilepsy, and other neuropsychiatric disorders.

The SOD1 Rat has been used extensively for drug discovery and basic research into ALS.

Taconic offers a panel of luciferase reporter mice to assay GPCR ligand binding and pathway activation in various tissues. Mice with CNS specific expression of CRE-Luc reporter can be used to isolate primary neurons (for in vitro studies) or for in vivo imaging studies to assay GPCR based signaling in the CNS. This platform can also provide rapid in vivo PK/PD profiling of compounds with quantitative data to compare pharmacological action.

Taconic offers the GFAP-Luc mouse which carries a luciferase reporter gene under the control of the GFAP promoter and provides an easy to use tool to study CNS damage. The reporter is inducible following injury to the CNS and the model is useful for studying changes in the health of the CNS.

Taconic offers several models for use in Experimental Autoimmune Encephalomyelitis (EAE), which is widely studied as an animal model of CNS demyelinating diseases, including Multiple Sclerosis (MS) and acute disseminated encephalomyelitis.

Like MS, EAE is characterized by infiltration of immune cells into the central nervous system (CNS) and demyelination. The two most widely-used methods to induce EAE are:

• Active induction by immunization
• Passive induction through adoptive transfer

Read our Insight (below) to learn more about these approaches.