Intraocular pressure in inbred mouse strains

PURPOSE: To develop a protocol to measure the intraocular pressure (IOP) of living mice and to determine the IOP of genetically different mouse strains. METHODS: Eyes of anesthetized animals were cannulated with a very fine fluid-filled glass microneedle. The microneedle was connected to a pressure transducer, and the pressure signal was analyzed with a computer system. Intraocular pressures of male C3H/He iota, C57BL/ 6 iota, A/iota, and BALB/c iota mice were determined. RESULTS: Differences in IOP were detected between genetically distinct mouse strains maintained in virtually identical environments. C3H/He iota was the strain with the highest average IOP (13.7 +/- 0.8 mm Hg). This strain average was 1.4 mm Hg higher than that for C57BL/6 iota (12.3 +/- 0.5 mm Hg; P = 0.14), 4.3 mm Hg higher than that for A/iota (9.4 +/- 0.5 mm Hg; P < 0.001), and 6 mm Hg higher than that for BALB/c iota (7.7 +/- 0.5 mm Hg; P < 0.001). CONCLUSIONS: The authors have developed an accurate and reliable procedure for measuring intraocular pressure in living mice. This procedure can detect IOP differences between groups of mice that differ by genotype

Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A–deficient mice

Mice lacking natriuretic peptide receptor A (NPRA) have marked cardiac hypertrophy and chamber dilatation disproportionate to their increased blood pressure (BP), suggesting, in support of previous in vitro data, that the NPRA system moderates the cardiac response to hypertrophic stimuli. Here, we have followed the changes in cardiac function in response to altered mechanical load on the heart of NPRA-null mice (Npr1–/–). Chronic treatment with either enalapril, furosemide, hydralazine, or losartan were all effective in reducing and maintaining BP at normal levels without affecting heart weight/body weight. In the reverse direction, we used transverse aortic constriction (TAC) to induce pressure overload. In the Npr1–/– mice, TAC resulted in a 15-fold increase in atrial natriuretic peptide (ANP) expression, a 55% increase in left ventricular weight/body weight (LV/BW), dilatation of the LV, and significant decline in cardiac function. In contrast, banded Npr1+/+ mice showed only a threefold increase in ANP expression, an 11% increase in LV/BW, a 0.2 mm decrease in LV end diastolic dimension, and no change in fractional shortening. The activation of mitogen-activated protein kinases that occurs in response to TAC did not differ in the Npr1+/+ and Npr1–/– mice. Taken together, these results suggest that the NPRA system has direct antihypertrophic actions in the heart, independent of its role in BP control

Nicotinamide benefits both mothers and pups in two contrasting mouse models of preeclampsia

Preeclampsia (PE), high blood pressure and protein in the urine in the last third of pregnancy, complicates about 1 in 20 human pregnancies, and it is one of the leading causes of pregnancy-related maternal deaths. The only definitive treatment, induced delivery, invariably results in premature babies. Blood pressure-lowering drugs help, but results in preventing preterm delivery and correcting the fetal growth restriction (FGR) that also occurs in PE have been disappointing. Here we show that feeding high doses of nicotinamide, a vitamin, improves the maternal condition, prolongs pregnancies, and prevents FGR in mice having PE-like conditions due to two contrasting causes. Because nicotinamide benefits both mothers and pups, it merits evaluation for preventing or treating PE in humans

Endothelin-1 critically influences cardiac function via superoxide-MMP9 cascade

Congestive heart failure develops in human patients and experimental animals when the left ventricle becomes dilated. In the present study, mice were generated having graded genetic levels of endothelin-1 from 20% normal to 350% normal by modifying the 3′ untranslated region of the endothelin-1 gene. The 20% and 65% hypomorphs develop dilated cardiomyopathy, whereas the 350% hypermorph has a hypertrophic heart. Increases in superoxide levels and overexpression of matrix metalloproteinase 9 (MMP9) are involved in the development of the dilated cardiomyopathy in the 20% hypomorph. Our results show that endothelin-1 is critical for maintaining normal cardiac contractile function, for controlling superoxide and Mmp9 levels, and for ensuring that the myocardium has sufficient collagen to prevent overstretching

New CC0\pi\ GENIE Model Tune for MicroBooNE

A novel tune has been made for the MicroBooNE experiment. The fit uses 4 new parameters within the GENIE v3.0.6 Monte Carlo program. Charged current pionless data from the T2K experiment was used. New uncertainties were obtained. These results will be used in future MicroBooNE analyses.Comment: 24 pages, 14 figure