ABSTRACT
The cage floor space recommended for a female rat with a litter is greater in the 8th edition of the Guide for the Care and Use of Laboratory Animals than in previous editions. As a result, research institutions using commonly available cages to house rats may not offer the recommended amount of space for a breeding pair and litter housed in the same cage. We evaluated breeding parameters in rats housed in cages with 143 in(2) (922.6 cm(2)) compared with 210 in(2) (1355 cm(2)) of floor space. Given the strains of rats typically used at our institution, a monogamous breeding pair and litter requires 164 in(2) (1058.1 cm(2)) of floor space according to the Guide. Pairs of breeding animals were housed in each type of cage; and average time between litters, number of litters born, percentage of litter weaned, numbers of pups born and weaned, and average weaning weights were evaluated. None of the breeding parameters evaluated differed according to the floor space of the cage in which the rats were housed.
Subject(s)
Animal Husbandry , Housing, Animal , Laboratory Animal Science , Rats , Animals , Breeding , Female , Male , WeaningABSTRACT
Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10(-7)) and 13% for RAB38/CTSC (P = 5.8 × 10(-7)). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria.
