Complete omission of exon 21 from Slc12a2 transcripts in mice results in hearing loss
Bibliographic record
Abstract
Hereditary hearing loss is highly heterogeneous. SLC12A2 is linked to autosomal dominant nonsyndromic hearing loss, DFNA78, with all the pathogenic variants affecting the exon 21. The gene encodes a cotransporter NKCC1 crucial for regulating intracellular osmotic pressure and producing endolymph in the cochlea. We generated two mouse strains with heterologous Slc12a2 variants in the splice site of the exon 21 ( Em1 : NM_009194.3:c.2912-2 A > G and Em2 : c.2912-4_2913del). Slc12a2 Em2/Em2 mice with complete skip of the exon 21 showed reduced endolymph on postnatal day 1 (P1), reduced stria vascularis (StV) and no auditory brainstem responses at 4 weeks. Reduced StV size was considered to be due to rebalance osmotic pressure, and upregulation of Cldn9 revealed by RNA-seq was considered as tissue response to repair the gaps from reduced cell sizes in the Slc12a2 Em2/Em2 cochlea. Female Slc12a2 Em2/+ mice also exhibited mild elevation of ABR thresholds in several sound frequencies. Slc12a2 Em1/Em1 mice showed normal hearing, presumably due to sufficient cotransporter activity from the 9 bases shorter transcript by cryptic splicing. Minigene assays indicated that a single nucleotide difference between humans and mice at the 5’ end of the exon 21 affects exon 21 splicing. Slc12a2 Em2 mouse is proposed as a model for studying DFNA78 pathology.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".