Functional rescue of the glomerulosclerosis phenotype in Mpv17 mice by transgenesis with the human Mpv17 homologue

Abstract

The germ line insertion of a defective retrovirus into the Mpv17 gene of mice is associated with a recessive phenotype. Mice homozygous for the integration develop glomerulosclerosis at a young age. The phenotype resembles human glomerulosclerosis in its physiological parameters as well as in histology. A human homologue of the Mpv17 gene has been identified, isolated and analyzed. We here show that this gene, which has a role in the production of reactive oxygen species, can rescue the phenotype of Mpv17 deficient mice when introduced by transgenesis. This provides formal proof for the hypothesis that the phenotype is caused by the loss of function of the Mpv17 gene. It also provides evidence for the functional conservation of the Mpv17 gene in mammals and points to a potential role of this gene in human kidney disease.

MicroRNAs as potential therapeutic targets in kidney disease

“…Mice lacking Mpv17 spontaneously develop kidney disease with glomerulosclerosis and interstitial diseases similar to CKD. 36–38 …”

Transgene Tiere

“…Man beschränkt sich auf das Einschleusen von Genen in bestimmte Zellen, was aber nicht zu einer Keimbahnintegration führt (Metsaranta u. Vuorio 1992, Iannaccone u. Scarpelli 1993, Woolf u. Fine 1993, Kappel et al 1994, Price u. Sisodia 1994, Schenkel et al 1995, Hartenstein et al 1996, Brinkmann et al 2002, Yuzaki 2005.…”

“…Selbst in nahezu infektionsfreien Mauskolonien lässt sich das C-reaktive Protein nie ganz auf Null regulieren (Ferber et al 1994). Ähnlich verhält sich der Metallothionin-Promotor, der selbst in nichtinduziertem Zustand eine gewisse Menge des Transgen-Proteins exprimieren lässt (Schenkel et al 1995). Die Induktion eines solchen Promotors ist oft sehr aufwändig und für die Tiere u. U. auch schädlich.…”

Restoration of normal bone development by human homologue of collagen type II (COL2A1) gene in Col2a1 null mice

“…Conservation of nucleotide sequence between the genes of evolutionary divergent species is a well-known phenomenon; however, the interspecific compatibility of biological role of the proteins is demonstrated only for a limited number of genes (Drabek et al, 1997;Paszty et al, 1997;Ryan et al, 1997;Schenkel et al, 1995;Wu et al, 1991). The compatibility of biological function of proteins between the species can have implications for generating transgenic animal models for human diseases and study the gene function during normal and pathological conditions.…”