Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Transgenic animal model of mood disorders

a transgenic animal and mood disorder technology, applied in the field of psychiatric illness markers, can solve the problems of lack of conceptually novel antidepressants, high cost to the us economy, and significant morbidity and excess mortality, and achieve the effect of stimulating phosphorylation (activation)

Inactive Publication Date: 2016-10-20
PROGENIKA BIOPHARMA SA +1
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a non-human transgenic animal with increased expression of a polynucleotide encoding a PTN polypeptide in at least one brain region. The transgenic animal exhibits one or more anxious and / or depressive-related behaviours, such as reduced time spent in open arms of an elevated plus maze, reduced time in central area in an open-field test, reduced time in light in a light-dark box test, increased latency to feed in a Novelty Suppressed Feeding Test, increased immobility time in tail suspension test, and reduced sucrose intake in sucrose intake task. The use of a more neuronal-specific promoter, the Thy promoter, is believed to contribute to the anxiety and depression-related behavior of the transgenic animal. The PTN transgenic animal may provide a better animal model of mood disorders and a more specific tool for studying the disease.

Problems solved by technology

Furthermore, these illnesses do not develop because of the alteration of one single gene but more likely due to changes in a group of genes, which makes them multi-factor illnesses.
Also, depression is associated with considerable morbidity and excess mortality (Sullivan et al., 2000; Belmaker and Agam, 2008).
The resulting cost to the US economy is estimated to be in the range of US $100 billion per year.
But in spite of these considerable financial incentives and the public health importance of treating depression, there is an absence of conceptually novel antidepressants on the market, reflecting the difficulties encountered in the development of new treatment strategies for this common and complex disorder.
Although these mono amine-based agents are potent antidepressants, and alterations in central monoamine function might contribute marginally to genetic vulnerability, the cause of depression is far from being a simple deficiency of central monoamines.
Animal models are widely used to study the neurobiological mechanisms of depression and anxiety but mouse models that mimic the full phenotypic spectrum of a psychiatric disorder, such as major depression, are virtually impossible.
However, it is difficult to prepare a model reflecting a human disease having a mechanism of development which is unknown, such as depression (Krishnan and Nestler, 2010).
A significant difficulty remains the translation of genetic association studies into models that are effective for evaluating the efficacy of candidate therapeutic compounds.
In particular, the complexity of the disorder means that it is not normally possible to predict whether a genetic alteration associated with the disorder has a causal role and will produce behavioural changes of relevance to depression and / or anxiety.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Transgenic animal model of mood disorders
  • Transgenic animal model of mood disorders
  • Transgenic animal model of mood disorders

Examples

Experimental program
Comparison scheme
Effect test

example 1

Analysis of Brain Tissue Using Microarray Data Analysis

[0142]Samples of post-mortem prefrontal cortex (Broadmann's Area 9) were obtained at autopsies performed in the Forensic Anatomical Institute, Bilbao, Spain, and stored at −80° C. The study was developed in compliance with policies of research and ethical review boards for post-mortem brain studies (Basque Institute of Legal Medicine, Bilbao). Deaths recorded as suicide were subjected to retrospective careful searching for previous medical diagnosis and treatment using examiner's information and records of hospitals and mental health centres. Depressed victims were selected according to the following criteria: suicide by violent method, lifetime diagnosis of Major Depression made according to DSM-IV and DSM-IV-R (American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4rd edition revised. American Psychiatric Association, Washington DC, 2000), absence of psychotropic or illegal drugs. Matched con...

example 2

Determination of PTN as a Biological Marker for Depression

[0146]Microarray results were investigated using quantitative PCR. Eighty three genes were selected for quantitative PCR to validate their mRNA expression on a larger sample set, by using Low Density Arrays (Annex 2). Seven genes (RPL10, B2M, ENO2, ZFP207, ACTB, GAPDH and NEFH) were selected to be used as reference genes. Validation was carried out using Low Density Arrays (Applied Biosystems) in a total of 40 prefrontal cortex samples (20 case and 20 control samples). This tool allowed the simultaneous interrogation of all the chosen target genes with two replicates for each gene using TaqMan® technology. Briefly, a 384-well microfluidic card is loaded with the selected gene expression assays. Each card is composed of eight sample-loading ports, each connected to 48 reaction wells. One microgram of RNA from each sample was reversed transcribed using a high-capacity cDNA archive kit (Applied Biosystems) and random primers. 25...

example 3

Validation by Western Blotting of PTN as a Biological Marker for Depression

[0148]The levels of PTN protein in human cerebral prefrontal cortex samples (Brodmann area 9) from individuals diagnosed with depression who died by suicide (n=23) and who had (n=11) or who had not (n=12) received antidepressant treatment and control subjects with no history of psychiatric illness who died accidentally (n=23), were validated by Western blotting with an antibody that specifically recognises said protein. The samples from depressive patients were paired with control samples on the basis of sex, age and post mortem delay. Target protein was quantified in pairs of subject with depression and the respective matched control. The relative content of each protein was calculated (percent change) in relation to in-gel triplicate standards (100%, pool of controls samples). This quantification procedure was assessed 2-3 times in different gels, and the resulting mean value of the target protein was used ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

A non-human transgenic animal having a polynucleotide encoding a PTN polypeptide, which polynucleotide is operably linked to a promoter, wherein said transgenic animal has greater than wild-type expression of the PTN polypeptide in at least one brain region, as well as related vectors, methods of producing transgenic animals, in vitro and in vivo screening methods for potential therapeutic agents, and methods for treating and diagnosing neuropsychiatric illnesses, particularly anxiety and depression, are disclosed.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This is a continuation of U.S. patent application Ser. No. 14 / 386,319, filed Sep. 18, 2014, which is the U.S. National Stage of International Application No. PCT / EP2013 / 055253, filed Mar. 14, 2013, which was published in English under PCT Article 21(2), which in turn claims the benefit of GB Application No. 1204816.1, filed Mar. 19, 2012, all of which are incorporated herein in its entirety.FIELD OF THE INVENTION[0002]The present invention relates to a marker for psychiatric illness, particularly mood disorders such as Major Depressive Disorder (MDD), Anxiety and Bipolar Disorder (BD), to animal models utilising the marker, to methods of screening for agents that affect the marker and which may have therapeutic potential, and to uses for treatment based on down-regulation of the marker expression and / or antagonism of its activity.BACKGROUND TO THE INVENTION[0003]Psychiatric disorders such as major depression, anxiety or bipolar disorder a...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): G01N33/68G01N33/50C12Q1/68
CPCG01N33/6896C12Q1/6883G01N33/5088C12Q2600/158C12Q2600/136G01N2800/304G01N2800/301G01N2800/50G01N2333/475A01K67/0275A01K2217/052A01K2217/206A01K2227/105A01K2267/0356C07K14/475C12N15/8509C12N2830/008G01N2500/10A01K2267/0306C07K16/22C12N15/1136C12Q2600/118G01N33/5058
Inventor ARTETA, DAVIDFERRER, MARCELOSIMON, LAUREANOMARTINEZ, ANTONIOURIBARRI, MARIA
Owner PROGENIKA BIOPHARMA SA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products