The genetic background of immune deficiency related mortality among Wetterhoun pups

Abstract

For about 17 years the Friese Staby and Wetterhoun association has been dealing with unexplained mortality among Wetterhoun pups. The clinical signs and the results of the random tests that have been performed over the years show that the affected pups are immune deficient. The syndrome shows great resemblance with the syndrome known as Severe combined immunodeficiency (SCID). SCID refers to a group of genetic disorders which all lead to a failing immune system and often result in death during infancy. It is characterized by T- and B-lymphocyte dysfunction or absence. In 2002 SCID has been found in the Jack Russell terrier and in this breed it is caused by a mutation in the DNA-dependent protein kinase catalytic subunit gene (DNA-PKcs). This mutation leads to a faulty V(D)J recombination [1]. This study shows that the affected Wetterhoun pups are suffering from SCID, but that this is not caused by the same mutation that causes SCID in the Jack Russell terrier. We also show that, of the genes involved in the V(D)J recombination, DNA PKcs, KU70, KU80, Artemis, DNA Ligase IV and XRCC4 are highly unlikely to be involved in SCID in the Wetterhoun. We could however not conclude the same for the genes RAG1 and RAG2. A mutation in either of these genes still remains a good possibility of being the cause of SCID in the Wetterhoun.