User:Rockpocket/Rad18
From Wikipedia, the free encyclopedia
E3 ubiquitin-protein ligase RAD18 is an enzyme that in humans is encoded by the RAD18 gene.[1][2][3]
The protein encoded by this gene is highly similar to S. cerevisiae DNA damage repair protein Rad18. Yeast Rad18 functions through its interaction with Rad6, which is a ubiquitin-conjugating enzyme required for post-replication repair of damaged DNA. Similar to its yeast counterpart, this protein is able to interact with the human homolog of yeast Rad6 protein through a conserved ring-finger motif. Mutation of this motif results in defective replication of UV-damaged DNA and hypersensitivity to multiple mutagens.[3]
Animal models
Model organisms have been used in the study of RAD18 function. A conditional knockout mouse line, called Rad18tm1a(EUCOMM)Wtsi,[4] was generated as part of the EUCOMM program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[5][6][7][8] Mice lacking Rad18 had no significant defects in viability or fertility,[9][10] therefore male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[5][11][12]
| Characteristic | Abnormal |
|---|---|
| Homozygote viability | No |
| Fertility | No |
| Body weight | Yes[13] |
| Hair follicle cycling | No |
| Anxiety | No |
| Modified SHIRPA | No |
| Grip strength | No |
| Dysmorphology | No |
| Indirect calorimetry | Yes[14] |
| Glucose tolerance test | No |
| Auditory brainstem response | No |
| DEXA | Yes[15] |
| Radiography | No |
| Body temperature | No |
| Eye morphology | No |
| Heart weight | No |
| Heart histology | No |
| Histology | No |
| Clinical chemistry | No |
| Plasma immunoglobulins | No |
| Haematology | No |
| Peripheral blood lymphocytes | No |
| Micronucleus test | Yes[12] |
| Salmonella infection | No |
| Citrobacter infection | No |
| All tests and analysis from [11][12] | |
Twenty four tests were carried out and four significant phenotypes were reported:[12]
- Mutant male mice had a decreased body weight compared to wildtype control mice.
- Mutant male mice showed increased activity, VO2 and energy expenditure, determined by indirect calorimetry.
- Dual-energy X-ray absorptiometry (DEXA) showed mutant male mice had a decrease in fat mass.
- A micronucleus test found a potential increase in DNA damage in mutant mice.