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Record W2099553437 · doi:10.1210/en.2009-0598

Disruption of the Single Copy Gonadotropin-Releasing Hormone Receptor in Mice by Gene Trap: Severe Reduction of Reproductive Organs and Functions in Developing and Adult Mice

2010· article· en· W2099553437 on OpenAlex
Sheng Wu, Michael D. Wilson, Ellen R. Busby, Emma R. Isaac, Nancy M. Sherwood

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueEndocrinology · 2010
Typearticle
Languageen
FieldMedicine
TopicHypothalamic control of reproductive hormones
Canadian institutionsUniversity of Victoria
FundersCanadian Institutes of Health ResearchNational Institutes of HealthJohns Hopkins University
KeywordsGNRHRHypogonadotropic hypogonadismBiologyInternal medicineEndocrinologyKisspeptinExonKnockout mouseGonadotropin-releasing hormoneReceptorHormoneLuteinizing hormoneGeneGeneticsMedicine

Abstract

fetched live from OpenAlex

Mutations in the GnRH receptor gene (GNRHR) can result in hypogonadotropic hypogonadism in humans. Unlike most mammals, mice lack a second form of GnRH (GnRH2) and a type 2 GnRH receptor. To determine whether the GnRH receptor is critical at all stages of reproduction and whether this receptor has additional physiological functions in developing and adult mice, we have generated mice from an embryonic stem cell line containing a retroviral vector with multiple stop codons inserted into intron 1 of the Gnrhr gene. This gene trap insertion resulted in the disruption of exon 2 and exon 3 of the Gnrhr gene. The insertion also contained a lacZ gene that was used as a reporter for GnRH receptor expression in these mice. This model has a similar phenotype to the clinical syndrome of hypogonadotropic hypogonadism. Null Gnrhr mice had small sexual organs, low levels of FSH, LH, and steroid hormones, failure of sexual maturation, infertility, and inability to respond to exogenous GnRH. However, the defective GnRH receptor did not prevent morula/blastocyst development, implantation, masculinization of fetal male mice, or maintenance of early pregnancy. The phenotype of this null Gnrhr mouse was more severe than models in the literature, including the N-ethyl-N-nitrosourea-induced Gnrhr mutant, the kisspeptin (Kiss1) knockout, and the kisspeptin receptor (Gpr54) knockout. In terms of gonadal morphology, adult gene trap-Gnrhr null mice demonstrate a complete cessation of reproduction and serve as an important model for understanding GnRH/GnRHR physiology.

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.

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)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.541
Threshold uncertainty score0.513

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.010
GPT teacher head0.238
Teacher spread0.227 · 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