title: Severe papillomavirus infection progressing to metastatic squamous cell carcinoma in bone marrow-transplanted X-linked SCID dogs.
abstract: Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma chain (gammac) gene and is identical clinically and immunologically to human XSCID, making it a true homologue of the human disease. Bone marrow-transplanted (BMT) XSCID dogs not only engraft donor T cells and reconstitute normal T-cell function but, in contrast to the majority of transplanted human XSCID patients, also engraft donor B cells and reconstitute normal humoral immune function. Shortly after our initial report of successful BMT of XSCID dogs, it soon became evident that transplanted XSCID dogs developed late-onset severe chronic cutaneous infections containing a newly described canine papillomavirus. This is analogous to the late-onset cutaneous papillomavirus infection recently described for human XSCID patients following BMT. Of 24 transplanted XSCID dogs followed for at least 1 year post-BMT, 71% developed chronic canine papillomavirus infection. Six of the transplanted dogs that developed cutaneous papillomas were maintained for >3 1/2 years post-BMT for use as breeders. Four of these six dogs (67%) developed invasive squamous cell carcinoma (SCC), with three of the dogs (75%) eventually developing metastatic SCC, an extremely rare consequence of SCC in the dog. This finding raises the question of whether SCC will develop in transplanted human XSCID patients later in life. Canine XSCID therefore provides an ideal animal model with which to study the role of the gammac-dependent signaling pathway in the response to papillomavirus infections and the progression of these viral infections to metastatic SCC.
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3900 Delancey St., Philadelphia, PA 19104, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Goldschmidt
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Kennedy
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Kennedy
authors.forename: Hang
authors.initials: H
authors.lastname: Yuan
authors.forename: David E
authors.initials: DE
authors.lastname: Holt
authors.forename: Margret L
authors.initials: ML
authors.lastname: Casal
authors.forename: Anne M
authors.initials: AM
authors.lastname: Traas
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mauldin
authors.forename: Peter F
authors.initials: PF
authors.lastname: Moore
authors.forename: Paula S
authors.initials: PS
authors.lastname: Henthorn
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Hartnett
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Weinberg
authors.forename: Richard
authors.initials: R
authors.lastname: Schlegel
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Felsburg
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology / Q000821:virology; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000662:veterinary / Q000821:virology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000821:virology*; D004285:Dogs; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000662:veterinary / Q000821:virology*; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis / Q000473:pathology; D030361:Papillomavirus Infections / Q000209:etiology / Q000473:pathology / Q000662:veterinary; D016511:Severe Combined Immunodeficiency / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000628:therapy / Q000662:veterinary / Q000821:virology*; D015398:Signal Transduction / Q000235:genetics; D012878:Skin Neoplasms / Q000473:pathology / Q000821:virology*; D013601:T-Lymphocytes / Q000473:pathology / Q000821:virology; D013997:Time Factors; D014183:Transplantation, Heterologous