Thrombin mutants with multiple alanine substitution of basic residues showed a progressively greater defect in inhibition potency.
Double mutant (TLR4lps-d/TLR9−/−) mice had an even greater defect in lung bacterial clearance, as compared to single mutant animals (p<0.05), with a 300-fold increase in CFU as compared to infected WT animals.
Furthermore, in Pima Indians, a greater defect in AIR was found in those who subsequently developed type 2 diabetes (7).
This is consistent with the PY1AA mutation exhibiting a greater defect in nuclear localization compared with the PY2AA mutation.
Also, one mutant (L494A, Y496A) showed a greater defect in di-Ub synthesis, perhaps marking the site where Ub binds as a substrate.
In grade II lesions both US and MR show oedema and fibrillar defects, and grade III lesions show a greater defect associated with haematoma and muscle.
Cause set aside, a greater defect in negative selection could allow a threshold to be crossed in which other mechanisms of maintaining tolerance are no longer sufficient to prevent disease.
The greater defect in the DT treated Ebi2-/- CD11c-DTR chimEbi2-/- CD11c-DTRt with a rolEbi2-/- CD11c-DTR supporting Ebi2-/- CD11c-DTRfor the polychimerasntisSRBconsistentell and GC responses.
