It is not the intention of this chapter to discuss in detail the many animal models which have been, and are still, in  use  in  investigating acne and  its  treatment. The reader is referred to the original references.

 

  In animals, many investigations  have been made to understand the physiology of the sebaceous glands and sebaceous gland-like organs and their pharmacological manipulation.

 

  Most animal experiments  have focussed  on the sebaceous gland, some on the pilosebaceous duct and very few on cutaneous bacteria and inflammation.

 

  There is no  perfect animal model for acne as a disease. Investigations on the hormonal  control of animal  sebaceous glands have been rewarding and do bear many similarities to human sebaceous gland function. These models include the sebaceous gland of a rat, hairless mice and male hairless hamsters. The sebaceous glands on the rabbit's ear4 and on the ventral side of the earlobes of the Syrian  hamster5 have also been used.

 

  Other organs with hormonal responses similar to the sebaceous glands of humans have been investigated and include the costovertebral organs, the Syrian golden hamster flank organ7 and the quail uropygial gland. Recently the most favoured  has been the ear of the Syrian hamster. Perhaps this is because their glands are large and similar to human follicles; their duct has an infundibulum,  a sebaceous duct,  multiple sebaceous lobules and a pilary unit, which enters below the gland.

 

  The  function and size of these animal sebaceous glands  and sebaceous gland-like structures,  are suppressed by oral anti-androgens and  so  parallel the human situation. However, there is no correlation after topical  treatment. Many of  these  animals  exhibit sebaceous gland suppression  after topical treatment of anti-androgen,  such as  17a-propylmesterotone  and spironolactone but humans infrequently and haphazardly show this suppression after topical application.11 There could be  several  reasons.  In most  of  these animals the sebaceous glands open onto, or almost onto, the skin surface and so are more likely to show suppression  after topical therapy. The human duct is long relative to the duct of the animals, with the possible exception of the sebaceous gland of the Syrian hamster. The skin bacteria of these animals differs from human. Propionibacterium acnes are almost unique to  man and P. acnes could  metabolize topical  anti-androgens. However, penetration differences between animal and human skin are the most likely explanation.

 

  There have been attempts to transplant full thickness human sebaceous glands  into nude  mice or  into hairless mice suppressed with antilymphotic  serum. One  difficulty of this model is the need for human tissue, the mortality of the grafted mice and rejection of the transplanted skin. However, when grafts are successful they have been shown to contain intact,  functioning sebaceous glands. Grafted human sebaceous glands become hyperplastic in response  to  androgen administration and microcomedones can  be produced, for example, with treatment with chlorinated hydrocarbons.

 

  This latter model is used for studying comedone formation but the most widely used comedone model is the rabbit ear model. This  is discussed in greater detail on page 12.  This  animal has a propensity to produce comedones  and does  so  quite  easily when stimulated with comedogenic substances. However, it is overpredictive when compared to man16 and many substances found to be comedogenic in the rabbit ear are not so, or less so, in humans. The Mexican hairless dog has plugged follicles on its back and flanks, which show clinical and histological similarities to comedones seen in man.17 The Rhino mouse has  many utricles, comedone-like structures which, like the rabbit ear, can be enhanced by comedogenic compounds and reduced by comedolytic drugs, such  as the retinoids (Figures

 

  P. acnes do  not usually occur  on the skin of most experimental animals but grafting of human skin onto athymic mice has been shown to produce no loss of surface P. acnes on the human skin and no colonization of the grafted skin with murine bacteria or vice versa.19 Such grafting techniques have shown the dependency of P. acnes on intact sebaceous glands, e.g. partial thick grafts  containing  few  sebaceous  glands  result  in  a marked loss of surface P. acnes .  This model  will  allow for a  greater degree  of in vivo experimentation on P. acnes, which could  not be performed on intact human skin.

 

  Inflammatory models for acne are limited. The injection  of callus  will  produce a late stage type  acne inflammatory response.20 However, these reactions are relatively  nonspecific and no technique, as yet,  exists for investigating the early stage of acne inflammation.

 

  Despite their shortcomings, some  of these models have helped in our understanding of the acne process and  in the  predicated benefit of certain oral  drugs, especially anti-androgens. They have been less helpful in predicting the  benefit of topically applied  acne therapies, especially  hormonal   therapies,  for  three reasons.