Table 3. Examples of phenotypes and mutations identified as part of the Harwell Ageing Screen.
| Pedigree | Phenotypic domain | Phenotype(s) | Age of detection (months) | Gene | CDS base change | Amino acid change | Supporting data | Current MGI alleles | Current MGI phenotypes | PubMed gene hits |
|---|---|---|---|---|---|---|---|---|---|---|
| MPC-96 | Deafness | Age-related hearing loss | ⩾9 | Slc4a10 | 1940T>C | L647P | a | 1 targeted null | BehaviourGrowth/sizeHomeostasisMortality/agingNervous System | 28 |
| MPC-102 | Neuro-degeneration | Gait abnormalities | ⩾12 | Eftud1 | 2948A>G | K983R | a | None | Glioma | 4 |
| MPC-151 | Deafness | (a) Progressive hearing loss(b) Reduced fat mass | (a) 3(b) 7 | Wars2 | 349G>T | V117L(+ splicing defects) | a, b | 2 targeted null | Mitochondrial functionGWAS adiposity | 7 |
| MPC-173 | VisionDeafness | (a) Deafness(b) Progressive corneal opacity | (a) ⩾3(b) ⩾9 | Ikzf2 | 1551C>A | H517Q | a | 2 targeted null | T-cell differentiationReduced growthIncreased mortalityAbnormal eyelid development | 51 |
| MPC-178 | Cardiac | Hypertrophic cardiomyopathy | 6 | Ecsit | 626G>T | N209I | a | 1 targeted null | Embryonic lethal | 28 |
| MPC-200 | SkinPathology | Epidermal and follicular hyperkeratosis | ⩾12 | Ces2F | 1286A>T | Q429L | a | None | None | 0 |
| MPC-201 | Vision | (a) Progressive reduction in visual acuity(b) Retinal degeneration | (a) ⩾12(b) ⩾12 | Idh3a | 685G>A | E229K | a | None | Retinitis Pigmentosa | 29 |
| MPC-205 | Deafness | Progressive hearing loss | ⩾6 | Ptprq | 5945+2T>C | Donor splice | a | 4 targeted | Postnatal deafness | 253 |
| MPC-205 | Renal Function | (a) Elevated creatinine/urea(b) Renal failure | (a) 6(b) 10–12 | Lama5 | 2651A>G | E884G | a, b | One gene trapFour targeted | DevelopmentRenal FunctionHom null lethal | 96 |
| MPC-227 | Body CompositionMusculo-skeletal | (a) Low-fat Mass(b) High-fat mass(c) Joint deterioration | (a) 3(b) 18(c) 15 | Acan | 5837C>T | A1946V | a | Three targeted null1 ENU inducedTwo spontaneous | CraniofacialGrowth/sizeAchondroplasia | 4,246 |
| MPC-236 | Neuro-behaviourNeurological | (a) Sleep abnormalities(b) Motor function deterioration | (a) 4(b) 12 | Vamp2 | 305T>A | I102N | a | Three targeted null | Synaptic vesicle functionGrowth/SizeMortality/AgeingHom null lethal | 624 |
| MPC-264 | Deafness | Progressive hearing loss | ⩾6 | Zfyve26 | 3943C>T | R1315X | a | 1 Endonuclease mediated | Spastic paraplegia | 16 |
ENU, N-ethyl-N-nitrosourea.
The candidate gene, base change and amino acid change are indicated. Supplementary Information details whether (a) if this was the only medium or high-confidence coding mutation in the minimal mapping region and (b) where genetic complementation with a knockout allele has been carried out. We list the existing alleles documented on MGI along with the current phenotypic associations derived from MGI. The number of PubMed hits obtained by the gene name or synonyms is also provided. Slc4a10, ENSMUST00000112480; Eftud1, ENSMUST00000039881; Wars2, ENSMUST00000004343; Ikzf2, ENSMUST00000027146; Ecsit, ENSMUST00000180180; Ces2F, ENSMUST00000076384; Idh3a, ENSMUST00000167866; Ptprq, ENSMUST00000050702; Lama5, ENSMUST00000015791; Acan, ENSMUST00000032835; Vamp2, ENSMUST00000021273; and Zfyve26, ENSMUST00000021547. MGI, Mouse Genome Informatics. GWAS, Genome Wide Association Study. CDS, Coding DNA Sequence.