Untersuchungen zu familiären und rassespezifischen ...

10 Summary
Sabrina Stritzel (2008)
Familial and breed specific hereditary diseases in dogs
Summary 166
The objective of this study was to examine canine diseases occurring basically in
certain breeds or families and so suggesting a genetic background. The role of a
couple of genes in the development of the following diseases appearing in definite
dog populations was examined in this work:
Canine pituitary-dependent hyperadrenocorticism
The cause of hyperadrenocorticism or Cushing’s disease is an excessive production
of cortisol by the adrenal cortex. In case of a secondary or pituitary-dependent
hyperadrenocorticism the origin is a pituitary tumor secreting ACTH and so
stimulating the adrenal cortex to permanent secretion of cortisol. Especially in smaller
dog breeds a frequent occurrence of this disease is recognized. In this work a breed
predisposition was confirmed for Dachshunds, Poodles and several Terrier breeds by
comparison of different studies describing a breed distribution between affected
dogs. In a family of wire-haired Dachshunds seventeen partly closely related animals
were affected. These diseased dogs were more closely related than the comparison
population. These findings suggest a hereditary disease. Familial Cushing’s disease
has only been described in Yorkshire and Dandie Dinmont Terriers yet. Because
these three breeds are connected in their breeding history, a common genetic
background can be assumed. An expression analysis of MDR1 (multi drug resistance
1) was performed in the liver of one of the affected Dachshunds. The performed
∆∆CT-analysis revealed an obvious increased relative expression of MDR1.
Assumedly this was caused by an up-regulation of MDR1 expression due to the
enduring excess of cortisol, which is transported by the MDR1 p-glycoprotein.
Sequence analysis of the coding regions of MDR1 of this dog did not reveal any
polymorphism in comparison to the reference sequence of the Boxer, so MDR1 is not
supposed be causative for the development of canine pituitary-dependent
hyperadrenocorticism.