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Record W1977325228 · doi:10.5339/qfarf.2012.aesnp10

Mice as animal models for human disease

2012· article· en· W1977325228 on OpenAlexaff
Zaher Hanna, Paul Jolicoeur

Bibliographic record

VenueQatar Foundation Annual Research Forum Volume 2012 Issue 1 · 2012
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAnimal Genetics and Reproduction
Canadian institutionsMontreal Clinical Research Institute
Fundersnot available
KeywordsDiseaseImmune systemImmunologyImmunodeficiencyWastingBiologyGenetically modified mouseCancerTransgeneMedicineVirologyPathologyGeneticsInternal medicineGene

Abstract

fetched live from OpenAlex

Background: Many human diseases lack validated animal models, hampering translational progress in several important disease areas. New and improved models can often be developed by recapitulating phenotypes related to those associated with human diseases. Objectives: Our lab has been interested in generating and characterizing several transgenic (Tg) animal models. These Tg animals were used to explore, on the cellular and molecular levels, the pathological mechanisms underlying several diseases, including immunological, neurodegenerative diseases, viral infections, cardiovascular disease, and cancer. Methods: Transgenes construction, analyzing techniques, and generation of Tg mice are as described in literature. Results: Examples of research projects that utilized animal models in our lab include: - Infectious diseases such as the acquired immunodeficiency syndrome (AIDS), which is caused by the human immunodeficiency virus type 1 (HIV-1). HIV-1 causes disease only in humans and chimpanzees. Thus, a major obstacle to explore the cellular and molecular mechanisms by which HIV-1 acts in vivo and to study how HIV-1 causes disease has been the lack of a small and cheap animal model. However, we have overcome the block to disease induction in rodents by generating Tg mice that express HIV-1 in the same immune cells that are normally infected in AIDS patients. These mice develop a severe AIDS-like disease leading to early death. Several pathological phenotypes, remarkably similar to those observed in HIV-1 infected individuals, were found. These included signs of growth retardation and wasting, atrophy of all lymphoid organs, preferential loss of CD4+ T cells, and interstitial nephritis and pneumonitis. More details will be presented. - Cancers such as leukemia and lymphoma as caused by murine leukemia viruses (MuLV) in inoculated mice. Their proviruses integrate in the vicinity of various genes involved in growth regulation, and act as insertion mutagens. We are using this retroviral insertion mutagenesis approach to identify novel oncogenes involved in T- or B-cell lymphomas induced by various MuLVs. We have succeeded in identifying novel oncogenes responsible for the onset of cancer. Among these oncogenes are members of Notch family, which are now under intense investigation to understand their role in inducing cancer. The details of these studies will be presented. Conclusions: It is likely that these novel Tg models will prove valuable in evaluating new pharmacological drugs, vaccines and disease therapies.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.596
Threshold uncertainty score0.852

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.054
GPT teacher head0.395
Teacher spread0.340 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations0
Published2012
Admission routes1
Has abstractyes

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