Premium
Rescuing of lethal phenotype of calcineurin A alpha knockout mice
Author(s) -
Reddy Ramesh Narayana,
Roberts Brian R,
Gooch Jennifer L
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.947.18
Subject(s) - calcineurin , endocrinology , medicine , knockout mouse , wild type , alpha (finance) , biology , podocin , kidney , transplantation , receptor , mutant , biochemistry , construct validity , nursing , gene , patient satisfaction , proteinuria , podocyte
Calcineurin is a calcium/calmodulin‐ dependent serine/threonine protein phosphatase discovered as a target of the immunosuppressant drug, cyclosporin A. Mice lacking α or β isoform of calcineurin have been useful in our understanding of the functions of calcineurin in the kidneys. While loss of the β isoform does not affect development or fertility, &alpha −/− mice routinely die between 3 and 4 weeks of age. Previously, we reported numerous developmental abnormalities in α −/− mice including reduced organ size and renal dysfunction. We now report the rescuing of the early lethality of α −/− mice by feeding the mice a powdered diet in gelatin. Groups of α−/− and wildtype mice were given supplemental food cups around 15 days and were fed a modified diet for 8 weeks. Weekly body weights and blood glucose levels were measured. At the end of 8 weeks postnatal, mice were sacrificed and serum, urine and tissue samples were collected. The α −/− mice regained body mass and had normal growth throughout the study period. Prior to rescue, α−/− mice were hypoglycemic consistent with malnutrition but feeding the modified diet led to slightly higher blood glucose levels than wildtype mice, suggesting an endocrine/metabolic abnormality. Despite rescue of the nutritional defect, serum BUN levels were significantly elevated with concomitant decrease in GFR in the alpha knockout mice compared to wildtype mice indicating impaired renal function.