title: Severe combined immunodeficiency in Frisian Water Dogs caused by a RAG1 mutation.
abstract: Mortality of pups at 8-12 weeks of age was frequently observed in Frisian Water Dogs. Blood parameters and clinical signs of newborns from three litters were monitored. Three pups from two litters showed strongly reduced levels of immunoglobulins and lymphocytes. These dogs were euthanized after first display of disease. Concurrent clinical and pathological features were consistent with a diagnosis of severe combined immunodeficiency (SCID). Defective V(D)J recombination is one of the causes of SCID in humans and animals. Eight genes involved in V(D)J recombination were investigated by segregation analysis of closely located microsatellite markers and by DNA sequence analysis. A nonsense mutation in the gene coding for V(D)J recombination factor RAG1 was identified in DNA from the cases at a position similar to that of nonsense mutations found in human SCID. It was concluded that SCID due to a mutation of RAG1 led to the high mortality.
authors.affiliation: Department of Clinical Sciences of Companion Animals, Utrecht University, Utrecht, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Verfuurden
authors.forename: F
authors.initials: F
authors.lastname: Wempe
authors.forename: P
authors.initials: P
authors.lastname: Reinink
authors.forename: P J S
authors.initials: PJ
authors.lastname: van Kooten
authors.forename: E
authors.initials: E
authors.lastname: Martens
authors.forename: R
authors.initials: R
authors.lastname: Gerritsen
authors.forename: J H
authors.initials: JH
authors.lastname: Vos
authors.forename: V P M G
authors.initials: VP
authors.lastname: Rutten
authors.forename: P A
authors.initials: PA
authors.lastname: Leegwater
mesh_terms: D000818:Animals; D001483:Base Sequence; D004285:Dogs / Q000235:genetics* / Q000276:immunology; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology
chemical_list: D018398:Homeodomain Proteins; C064658:RAG-1 protein