one standard mouse
- Thread starter leopold
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depends what the research is about.
c. a transgenic mouse.
Basically it is impossible at the moment to get a paper in a good journal with just a NMRI mouse (inbred mouseline, let's say it is a normal mouse).
You need a transgenic line with a interesting phenotype.
This can lead to politics in research groups and in between research groups. Which student gets assigned the interesting transgenic mouseline? It can make and brake careers. Nothing to do with how good you are.
Basically it is impossible at the moment to get a paper in a good journal with just a NMRI mouse (inbred mouseline, let's say it is a normal mouse).
You need a transgenic line with a interesting phenotype.
This can lead to politics in research groups and in between research groups. Which student gets assigned the interesting transgenic mouseline? It can make and brake careers. Nothing to do with how good you are.
Why is it always mice that are used?
The mouse is a vertebrate and can therefore be used as a model for vertebrate development.
The mouse is small and therefore cheap to keep.
The mouse breeds easily.
In the old days it was therefore easy to bread certain traits.
Nowadays it is easy to make transgenic mouselines. It's not always so easy with other animals.
So many people were using the mouse that it had many more genes sequenced than other model systems, and later it was one of the first organisms of which the entire genome was sequenced.
it's cute and fluffy.
And probably there are more reasons.
The mouse is small and therefore cheap to keep.
The mouse breeds easily.
In the old days it was therefore easy to bread certain traits.
Nowadays it is easy to make transgenic mouselines. It's not always so easy with other animals.
So many people were using the mouse that it had many more genes sequenced than other model systems, and later it was one of the first organisms of which the entire genome was sequenced.
it's cute and fluffy.
And probably there are more reasons.
Because Mice own this planet, Earth...they have been experementing on us humans in the test tubes...
I mean other than the pan-dimensional beings.
otherwise the answer is 42.
SpuriousMonkey:
Do you know anything about Regeneron and this:
"Regeneron scientists have recently developed a novel high-throughput approach that is amenable to creating many preclinical disease models a year. These approaches have been grouped under the term “Velocigene,” allowing for the high throughput assignment of function to genes. Velocigene uses a proprietary and high-throughput process to ablate genes (creating gene “knockouts”) or introduce extra gene copies (creating “transgenics”), rapidly producing mammalian models for elucidating the function of the altered genes. Regeneron developed Velocigene to “functionize” the large numbers of newly identified genes resulting from the sequencing of the human genome, so as to determine rapidly which of these many genes represent validated therapeutic targets for pharmaceutical drug development."
And
"Breakthrough platform for creating fully-human, therapeutic monoclonal antibodies
The VelocImmune mouse was created using Regeneron’s proprietary VelociGene technology to precisely replace only the variable regions of mouse immune loci (heavy chain V, D, and J segments, and light chain V and J segments) with corresponding human variable sequences in situ, while leaving the normal mouse constant regions intact. Previously engineered human monoclonal antibody (HuMAb) mice make antibodies with human constant regions and contain incomplete transcriptional controls potentially resulting in inefficient protein-to-protein interactions in signal transduction cascades critical for the generation of high-affinity antibodies. Unlike current HuMAb mice, VelocImmune mice have immune systems that appear identical to normal mice..."
More at: www.regeneron.com
I am over my head here, but just bought some of their stock after hearing and seeing the slides they presented at JP Morgan's 25 conference in San Fransico (Live via internet). This was only small part of reason why - Solid pipeline with 14 early stage drugs showing promiss was bigger factor.
Today is last day of conference - I have bought into 9 new drug developers and understand this one the least. - I am getting grogy after learning so much -5 parallel pressentation for four days with a couple hundered presentation. Most important annual event in this field, MHO. I can jump from room to room better than if I were in San Fransico!
Do you know anything about Regeneron and this:
"Regeneron scientists have recently developed a novel high-throughput approach that is amenable to creating many preclinical disease models a year. These approaches have been grouped under the term “Velocigene,” allowing for the high throughput assignment of function to genes. Velocigene uses a proprietary and high-throughput process to ablate genes (creating gene “knockouts”) or introduce extra gene copies (creating “transgenics”), rapidly producing mammalian models for elucidating the function of the altered genes. Regeneron developed Velocigene to “functionize” the large numbers of newly identified genes resulting from the sequencing of the human genome, so as to determine rapidly which of these many genes represent validated therapeutic targets for pharmaceutical drug development."
And
"Breakthrough platform for creating fully-human, therapeutic monoclonal antibodies
The VelocImmune mouse was created using Regeneron’s proprietary VelociGene technology to precisely replace only the variable regions of mouse immune loci (heavy chain V, D, and J segments, and light chain V and J segments) with corresponding human variable sequences in situ, while leaving the normal mouse constant regions intact. Previously engineered human monoclonal antibody (HuMAb) mice make antibodies with human constant regions and contain incomplete transcriptional controls potentially resulting in inefficient protein-to-protein interactions in signal transduction cascades critical for the generation of high-affinity antibodies. Unlike current HuMAb mice, VelocImmune mice have immune systems that appear identical to normal mice..."
More at: www.regeneron.com
I am over my head here, but just bought some of their stock after hearing and seeing the slides they presented at JP Morgan's 25 conference in San Fransico (Live via internet). This was only small part of reason why - Solid pipeline with 14 early stage drugs showing promiss was bigger factor.
Today is last day of conference - I have bought into 9 new drug developers and understand this one the least. - I am getting grogy after learning so much -5 parallel pressentation for four days with a couple hundered presentation. Most important annual event in this field, MHO. I can jump from room to room better than if I were in San Fransico!
Last edited by a moderator:
There is a long way from a transgenic mouseline to a drug. A transgenic mouseline will have an unknown phenotype which first needs to be analyzed. I can assure you this costs time and money if done properly. I would need to read more on their high throughput method to really say anything, and still, I am not an expert in these things.
Is the highthroughput method about making the models or analyzing the models or both? Even after analysis there is no clear path to a new drug. Each instance will be different.
Or are they planning to sell the mouselines?
haven't givent the other things you mentioned any thought yet.
spurious is right, its a long road from transgenic mice to drugs. Just the approval for testing in animals and then later for testing in human clinical trials is a big step. (IRB boards for human testing are usually pretty strict).
Other than that, I'm not an expert in this field (monoclonal antibodies and transgenic mice).
All I can say is that identifying a gene that may be a good therapeutic target for a disease is not as simple a proposition as it sounds. There may be several genes which appear to result in common defects but have different paths to producing one set of symptoms, there may be downstream effects of certain combinations of genes, the disease may be due to absence of a process rather than presence of a gene product. It may be due to post-translational modification of the gene product. There are a lot of ifs and maybes.
There may even be several different ways to tackle the same problem.
e.g.
diabetes:
using spleen cells:
http://www.boston.com/news/nation/articles/2003/11/14/juvenile_diabetes_cured_in_lab_mice/
by tweaking neuronal responses:
http://www.canada.com/nationalpost/news/story.html?id=a042812e-492c-4f07-8245-8a598ab5d1bf
so ultimately it may depend on whichever method is cheapest plus most effective. A long term investment.
Other than that, I'm not an expert in this field (monoclonal antibodies and transgenic mice).
All I can say is that identifying a gene that may be a good therapeutic target for a disease is not as simple a proposition as it sounds. There may be several genes which appear to result in common defects but have different paths to producing one set of symptoms, there may be downstream effects of certain combinations of genes, the disease may be due to absence of a process rather than presence of a gene product. It may be due to post-translational modification of the gene product. There are a lot of ifs and maybes.
There may even be several different ways to tackle the same problem.
e.g.
diabetes:
using spleen cells:
http://www.boston.com/news/nation/articles/2003/11/14/juvenile_diabetes_cured_in_lab_mice/
by tweaking neuronal responses:
http://www.canada.com/nationalpost/news/story.html?id=a042812e-492c-4f07-8245-8a598ab5d1bf
so ultimately it may depend on whichever method is cheapest plus most effective. A long term investment.
Think Faustman is the lady with 2 pages in the current issue Portugese issue of Scientific American She got rapped hard by piers who could not reproduce this work but now others have.
I am well aware of the complex three phase progess to get a new drug to market, and how few make it even after great expenditures. In case of Regeneron they have partnered out about half of their pipeline, even in early stages to "big Pharma," and the "up front" funds are more than adequate for entire program for awhile (milestone payments, if received, will carry all thru Phase 3) If half get to Phase 3 and a couple to market, they will do well.