Model Description

Imiquimod (IMQ) is a ligand for TLR7 and TLR8 and  it's original use was for the treatment of  non-melanoma skin cancers. The topical application of IMQ on the shaved back skin of the mouse induces a psoriasis-like skin condition exhibiting most of the human psoriasis pathology characteristic features including acanthosis, parakeratosis,  infiltration of immune cells and involvement of the IL23/ IL17/ IL22 pathway. The pathology features regress upon topical application of cortocosteroids.

TghIL17A is a BAC transgenic line generated through microinjection of a DNA fragment containing the coding sequences of hIL17A  flanked by  several kb of its 5’ and 3’ regulatory sequences. Upon stimulation human IL17A is expressed and contributes to the development of the induced pathology. 

Preclinical efficacy evaluation

Stydy design

IMQ is applied on the shaved back of the mice daily for 5 consequtive days. Signs of psoriasis appear from day 2 onwards as erythema, scaling and skin thickening. The severity of the signs is daily assessed. The experimental design  always includes an uninduced control group (vaseline treated), a negative therapeutic control group (imiquimod-induced without treatment) and a  positive therapeutic control group (corticosteroids).

Read-out parameters

  • Daily body weight measurements reflecting the general health status 
  • Daily in vivo scoring of skin erythema, skin scaling and skin thickness reflecting the progress of the pathology
  • Spleen weight to body weight ratio measured at the end of the study reflecting the disease related immune activation
  • Histopathological scoring at the end of the study recapitulating the pathology status

 

Figure 1: Representative graphs of in vivo measurments of TghIL17A animals with IMQ-induced psoriasis. Treatment with corticosteroids (Butavate & Retavate) reverses disease symptoms.

Figure 2: Representative graphs of ex-vivo of TghIL17A animals with IMQ-induced psoriasis. Treatment with corticosteroids (Butavate & Retavate) reverses disease symptoms.

Figure 3: Representative graphs of histopathological assesment of TghIL17A animals with IMQ-induced psoriasis. Treatment with corticosteroids (Butavate & Retavate) reverses disease symptoms.

 

Vaseline                                                            IMQ 
    

IMQ/Retavate                                                 IMQ/Butavate
    

Figure 4: Representative graphs of histopathological images of TghIL17A animals with IMQ-induced psoriasis. Treatment with corticosteroids (Butavate & Retavate) reverses disease symptoms.