التفاصيل البيبلوغرافية
| العنوان: |
Mice with a Brd4 mutation represent a new model of nephrocalcinosis |
| المؤلفون: |
Gorvin, CM, Loh, NY, Stechman, MJ, Falcone, S, Hannan, FM, Ahmad, BN, Piret, SE, Reed, AAC, Jeyabalan, J, Leo, P, Marshall, M, Sethi, S, Bass, P, Roberts, I, Sanderson, J, Wells, S, Hough, TA, Bentley, L, Christie, PT, Simon, MM, Mallon, A-M, Schulz, H, Cox, RD, Brown, MA, Huebner, N, Brown, SD, Thakker, RV |
| سنة النشر: |
2019 |
| مصطلحات موضوعية: |
Male, Transcription, Genetic, Mutation, Missense, Nuclear Proteins, Apoptosis, Kidney, Chromosomes, Mammalian, Article, Disease Models, Animal, Mice, Nephrocalcinosis, Phenotype, Genetic Loci, Chromosome Segregation, Exome Sequencing, Animals, Female, Amino Acid Sequence, Transcription Factors |
| الوصف: |
Nephrolithiasis (NL) and nephrocalcinosis (NC), which comprise renal calcification of the collecting system and parenchyma, respectively, have a multifactorial etiology with environmental and genetic determinants and affect ∼10% of adults by age 70 years. Studies of families with hereditary NL and NC have identified >30 causative genes that have increased our understanding of extracellular calcium homeostasis and renal tubular transport of calcium. However, these account for 80% penetrance in 152 progeny. The calcification consisted of calcium phosphate deposits in the renal papillae and was associated with the presence of the urinary macromolecules osteopontin and Tamm-Horsfall protein, which are features found in Randall's plaques of patients with NC. Genome-wide mapping located the disease locus to a ∼30 Mbp region on chromosome 17A3.3-B3 and whole-exome sequence analysis identified a heterozygous mutation, resulting in a missense substitution (Met149Thr, M149T), in the bromodomain-containing protein 4 (BRD4). The mutant heterozygous (Brd4+/M149T ) mice, when compared with wild-type (Brd4+/+ ) mice, were normocalcemic and normophosphatemic, with normal urinary excretions of calcium and phosphate, and had normal bone turnover markers. BRD4 plays a critical role in histone modification and gene transcription, and cDNA expression profiling, using kidneys from Brd4+/M149T and Brd4+/+ mice, revealed differential expression of genes involved in vitamin D metabolism, cell differentiation, and apoptosis. Kidneys from Brd4+/M149T mice also had increased apoptosis at sites of calcification within the renal papillae. Thus, our studies have established a mouse model, due to a Brd4 Met149Thr mutation, for inherited NC. © 2019 American Society for Bone and Mineral Research. |
| اللغة: |
English |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::9c54779c6d4c53398e8c393e1cacdb82
https://europepmc.org/articles/PMC6658219/ |
| حقوق: |
OPEN |
| رقم الأكسشن: |
edsair.pmid.dedup....9c54779c6d4c53398e8c393e1cacdb82 |
| قاعدة البيانات: |
OpenAIRE |
