Claudin 3 CRISPR Knockout Mice are Healthy and Fertile
Bibliographic record
Abstract
Claudins regulate the passage of ions and solutes between neighboring cells through tight junctions. The nephron is the functional unit of the kidney that filters the blood and removes excess water, salts and wastes. The filtering properties of the nephron are determined by the unique combination of claudins expressed within each segment. Claudins are expressed in the nephric duct in advance of kidney function. Nephric duct derivatives undergo branching morphogenesis and ultimately each branch tip induces a mesenchymal‐to‐epithelial transition event required for nephron formation. In the chick embryo, a reagent that specifically removes Claudin 3 and 4 from tight junctions blocked nephric duct formation. This led us to hypothesize that claudins are required for kidney development in the mouse. Claudin‐4 knockout mice do not have an embryonic phenotype, therefore, Claudin‐3 was prioritized for investigation. Claudin‐3 compound heterozygote mice were created using the CRISPR/Cas9 system of genome editing. Male and female founder mice were generated with distinct frameshift mutations in both Claudin‐3 alleles. Neither of these founders showed an obvious phenotype. Pups derived from mating these founders appeared grossly normal. Histological analysis of the kidneys did not reveal a nephron phenotype. In conclusion, Claudin‐3 null mice generated by CRISPR/Cas9 are healthy and fertile. We hypothesize that the lack of Claudin‐3 is compensated by other claudins. This will be tested by creating double knockouts using the CRISPR/Cas9 system, which would be predicted to create a more severe phenotype and allow further understanding of the important role of claudins during kidney development.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.014 | 0.006 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".