Abstract | BACKGROUND: METHODS: We characterized the phenotypes of six- and 12-week-old Aprt-/- Opn-/-, Aprt-/- Opn+/+, Aprt+/+ Opn-/-, and Aprt+/+ Opn+/+ male and female mice using biochemical, histologic, immunohistochemical, and in situ hybridization techniques. RESULTS: At 6 weeks of age, there was no difference in phenotype between double knockout and Aprt knockout mice. At 12 weeks, there was increased adenine and DHA excretion, renal crystal deposition, and inflammation in double knockout versus Aprt knockout male mice. Double knockout and Aprt knockout female mice at 12 weeks had less pathology than their male counterparts, but kidneys from double knockout females showed more inflammation compared with Aprt knockout females; both genotypes had similar levels of DHA crystal deposition. CONCLUSION: We conclude that (1) OPN is a major inhibitor of DHA crystal deposition and inflammation in male mice; and (2) OPN is a major modifier of the inflammatory response but not of crystal deposition in female mice. Thus, separate mechanisms appear responsible for the tissue changes seen in DKO males versus females.
|
Authors | Hilary J Vernon, Christine Osborne, Eleni G Tzortzaki, Min Yang, Jianmen Chen, Susan R Rittling, David T Denhardt, Steven Buyske, Sharon B Bledsoe, Andrew P Evan, Lynette Fairbanks, H Anne Simmonds, Jay A Tischfield, Amrik Sahota |
Journal | Kidney international
(Kidney Int)
Vol. 68
Issue 3
Pg. 938-47
(Sep 2005)
ISSN: 0085-2538 [Print] United States |
PMID | 16105024
(Publication Type: Journal Article)
|
Chemical References |
- RNA, Messenger
- Sialoglycoproteins
- Spp1 protein, mouse
- Osteopontin
- Collagen
- Xanthine Dehydrogenase
- Adenine Phosphoribosyltransferase
|
Topics |
- Adenine Phosphoribosyltransferase
(genetics)
- Animals
- Body Weight
- Collagen
(metabolism)
- Crystallization
- Female
- Fibrosis
- Growth
- In Situ Hybridization
- Kidney
(metabolism, pathology)
- Kidney Calculi
(genetics, pathology, physiopathology)
- Macrophages
(enzymology, pathology)
- Male
- Mice
- Mice, Inbred Strains
- Mice, Knockout
- Osteopontin
- Phenotype
- RNA, Messenger
(analysis)
- Severity of Illness Index
- Sex Characteristics
- Sialoglycoproteins
(genetics)
- Survival Rate
- Urine
(chemistry)
- Xanthine Dehydrogenase
(genetics)
|