The genetic control of sialadenitis versus arthritis in a NOD.QxB10.Q F2 cross.
The non-obese diabetic (NOD) mouse spontaneously develops diabetes and sialadenitis. The sialadenitis is characterized by histopathological changes in salivary glands and functional deficit similar to Sjögren's syndrome. In humans, Sjögren's syndrome could be associated with other connective tissue disorders, such as rheumatoid arthritis. In the present study the genetic control of sialadenitis in mice was compared to that of arthritis. We have previously reported a NOD locus, identified in an F2 cross with the H2(q) congenic NOD (NOD.Q) and C57BL/10.Q (B10.Q) strains, that promoted susceptibility to collagen-induced arthritis. The sialadenitis in NOD.Q showed a similar histological phenotype as in NOD, whereas no submandibular gland infiltration was found in B10.Q. The development of sialadenitis was independent of immunization with type II collagen and established arthritis. To identify the genetic control of sialadenitis, a gene segregation experiment was performed on an (NOD.QxB10.Q)F2 cross and genetic mapping of 353 F2 mice revealed one significant locus associated with sialadenitis on chromosome 4, LOD score 4.7. The NOD.Q allele-mediated susceptibility under a recessive inheritance pattern. The genetic control of sialadenitis seemed to be unique in comparison to diabetes and arthritis, as no loci associated with these diseases have been identified at the same location.
Johansson
Asa C M
AC
Section for Medical Inflammation Research, University of Lund, Lund, Sweden. Asa.Johansson@inflam.lu.se
Nakken
Britt
B
Sundler
Martin
M
Lindqvist
Anna-Karin B
AK
Johannesson
Martina
M
Alarcón-Riquelme
Marta
M
Bolstad
Anne Isine
AI
Humphreys-Beher
Michael G
MG
Jonsson
Roland
R
Skarstein
Kathrine
K
Holmdahl
Rikard
R
D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000235:genetics*; D002874:Chromosome Mapping; D002875:Chromosomes; D003433:Crosses, Genetic; D005260:Female; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010641:Phenotype; D012793:Sialadenitis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D013363:Submandibular Gland / Q000473:pathology
D000949:Histocompatibility Antigens Class II; C407099:I-A g7 antigen