The mitochondrial and kidney disease phenotypes of kd/kd mice under germfree conditions

Abstract

Interstitial nephritis occurs spontaneously in kd/kd mice, but the mechanisms leading to this disease have not been fully elucidated. The earliest manifestation of a phenotype is the appearance of ultrastructural defects in the mitochondria of mice as young as 42 days of age. To examine the influence of the environment on the phenotype, homozygous B6.kd/kd mice were transferred from specific pathogen-free (SPF) conditions to a germfree (GF) environment, and the development of the disease was observed. The GF state resulted in a highly significant reduction in the frequency of tubulointerstitial nephritis. In addition, GF conditions markedly reduced the appearance of the mitochondrial phenotype, with no sign of mitochondrial abnormalities in GF mice of up to 155 days of age. These results suggest that environmental factors are involved in the progression of all known manifestations of this disease phenotype.

CoQ10 supplementation: a new treatment modality in steroid-resistant nephrotic syndrome with unknown molecular etiology

“…[40,41] An autoimmune response involves both the tubular interstitium and glomeruli, causing the death of glomerular podocytes were demostrated by ultrastructural analysis in mitochondria of mutant mice. [42,43] Our biopsy findings included mostly sclerotic glomerules and tubulointerstisyel changes, similar to literatue. Also, similar findings were reported in a murine model, in which animals spontaneously develop proteinuria and renal disease associated with the presence of numerous dysmorphic mitochondria in all cell types, and histologically collapsing glomerulopathy.…”

Collapsing Glomerulopathy

“…If human equivalents for these susceptibility genes exist, then interventions to decrease environmental stress could affect the development or progression of CG in patients who harbor these genes. A proof of this concept has been demonstrated already in kd/kd mice, in which caloric restriction or birthing into a germ-free environment rather than a specific pathogen-free environment ameliorates CG in this model (111).…”

Genetics of Coenzyme Q10 Deficiency

“…It is possible that the residual amount of CoQ 10 produced in the patients (a complete block of the biosynthetic pathway is embryonically lethal [Levavasseur et al, 2001;Peng et al, 2008]) may determine the clinical phenotype, but there are no comprehensive studies on this issue. Environmental factors also play an important role as demonstrated by studies performed in mice [Fernandes et al, 1978;Hallman et al, 2006].…”