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11.
Jamie Lovaglio James E Artwohl Christopher J Ward Thomas GH Diekwisch Yoshihiro Ito Jeffrey D Fortman 《Comparative medicine》2014,64(2):115-120
Three mice (2 male, 1 female; age, 5 to 16 mo) from a mouse line transgenic for keratin 14 (K14)-driven LacZ expression and on an outbred Crl:CD1(ICR) background, were identified as having distended abdomens and livers that were diffusely enlarged by numerous cysts (diameter, 0.1 to 2.0 cm). Histopathology revealed hepatic cysts lined by biliary type epithelium and mild chronic inflammation, and confirmed the absence of parasites. Among 21 related mice, 5 additional affected mice were identified via laparotomy. Breeding of these 5 mice (after 5 mo of age) did not result in any offspring; the K14 mice with polycystic livers failed to reproduce. Affected male mice had degenerative testicular lesions, and their sperm was immotile. Nonpolycystic K14 control male mice bred well, had no testicular lesions, and had appropriate sperm motility. Genetic analysis did not identify an association of this phenotype with the transgene or insertion site.Abbreviations: K14, keratin 14 promoter; LacZ, bacterial β-galactosidase LacZ reporter; Lsamp, mouse limbic system-associated membrane proteinPolycystic disease is a multiorgan disorder and is the most common genetic life-threatening disease in people, affecting more than 600,000 Americans.16 Cystic liver disease in people typically is associated with polycystic kidney disease22,36 but can exist in its absence. Currently, 2 autosomal dominant genes (PRKCSH and SEC63P) that cause a human polycystic liver disease condition without renal involvement have been identified.4-6,13Numerous rodent models of polycystic kidneys with concurrent polycystic liver exist.8,34,39,40 However, effective models of polycystic liver without polycystic kidneys would be useful to address clinical and mechanistic issues of polycystic liver not associated with polycystic kidneys.6,31Here we report multiple cases of a spontaneous polycystic liver phenotype without a kidney phenotype in a transgenic mouse line. We also describe the effect of the transgene on disease expression and our attempts to develop this stock as an animal model. 相似文献
12.
Thomas GH; Newbern EC; Korte CC; Bales MA; Muse SV; Clark AG; Kiehart DP 《Molecular biology and evolution》1997,14(12):1285-1295
Many structural, signaling, and adhesion molecules contain tandemly
repeated amino acid motifs. The alpha-actinin/spectrin/dystrophin
superfamily of F-actin-crosslinking proteins contains an array of triple
alpha-helical motifs (spectrin repeats). We present here the complete
sequence of the novel beta-spectrin isoform beta(Heavy)- spectrin (beta H).
The sequence of beta H supports the origin of alpha- and beta-spectrins
from a common ancestor, and we present a novel model for the origin of the
spectrins from a homodimeric actin-crosslinking precursor. The pattern of
similarity between the spectrin repeat units indicates that they have
evolved by a series of nested, nonuniform duplications. Furthermore, the
spectrins and dystrophins clearly have common ancestry, yet the repeat unit
is of a different length in each family. Together, these observations
suggest a dynamic period of increase in repeat number accompanied by
homogenization within each array by concerted evolution. However, today,
there is greater similarity of homologous repeats between species than
there is across repeats within species, suggesting that concerted evolution
ceased some time before the arthropod/vertebrate split. We propose a
two-phase model for the evolution of the spectrin repeat arrays in which an
initial phase of concerted evolution is subsequently retarded as each new
protein becomes constrained to a specific length and the repeats diverge at
the DNA level. This evolutionary model has general applicability to the
origins of the many other proteins that have tandemly repeated motifs.
相似文献
13.
Renal glomerular evolution in Antarctic notothenioid fishes 总被引:2,自引:0,他引:2
Light and electron microscopy were used to document the degree of glomerular development in 10 species of Antarctic notothenioid fishes. When combined with results of previous studies, data revealed that 16 of 20 species inhabiting subzero sea water were aglomerular. One subantarctic and two temperate species were pauciglomerular, and an additional temperate species had a moderate number of glomeruli. Renal corpuscles were variable in number and diameter among the pauciglomerular species, and most had few patent glomerular capillaries. Radiolabelled markers indicated that the glomerular filtration rate was low in the pauciglomerular Notothenia angustata , ranging from 0.005 to 0.124 ml h−1 kg−1 in eight specimens. Arterial perfusion of Microfil demonstrated that arteries supplying aglomerular and pauciglomerular kidneys were confined largely to the periphery of the organ, and glomerular capillaries were absent or few in number. As ancestral notothenioids probably had glomerular kidneys, data from 20–25% of the fauna suggest that there has been an evolutionary loss of glomeruli in many species. The pattern of glomerular reduction is consistent with the hypothesis that the selective advantage of aglomerularism is in the urinary conservation of small molecular weight antifreeze glycopeptide compounds that are vital to survival in sub-zero Antarctic waters. 相似文献
14.
15.
Previously, we developed a balloon transducer to measure the constraint of the pericardium (i.e., pericardial pressure) on the surface of the heart. It was validated physiologically in that it was shown to measure a pressure equal to the difference between the left ventricular end-diastolic pressure measured before and after pericardiectomy at the same left ventricular volume. To define its static operating characteristics, we loaded the balloon nonuniformly with weights that covered fractions of the balloon surface and found that the balloon accurately recorded the average stress if the stress was applied over at least 23% of its surface. To test its performance when curved, we placed it in large and small cylinders (minimum diameter 31 mm) and found that the balloon accurately recorded the stress. To define its dynamic operating characteristics, we applied sinusoidal stresses and found that its frequency response was limited only by that of the connecting catheter. When better dynamic response is required, we introduce a micromanometer-tipped catheter to obtain a unity-gain frequency response that is flat to 200 Hz. 相似文献
16.
Annemarie MM Vlaar Marinus JPG van Kroonenburgh Alfons GH Kessels Wim EJ Weber 《BMC neurology》2007,7(1):27
Background
Parkinson's disease (PD) is the second most common neurodegenerative disorder. One of the most widely used techniques to diagnose PD is a Single Photon Emission Computer Tomography (SPECT) scan to visualise the integrity of the dopaminergic pathways in the brain. Despite this there remains some discussion on the value of SPECT in the differential diagnosis of PD. We did a meta-analysis of all the existing literature on the diagnostic accuracy of both pre- and post-synaptic SPECT imaging in the differential diagnosis of PD. 相似文献17.
Leshinsky-Silver E Landau Z Unlubay S Bistrizer T Zung A Tenenbaum-Rakover Y Devries L Lev D Hanukoglu A 《Hormone research》2006,66(2):73-78
BACKGROUND/AIMS: Isolated aldosterone biosynthesis defect causing congenital hyperreninemic hypoaldosteronism with otherwise normal adrenal function usually results from aldosterone synthase deficiency. Patients present with manifestations of mineralocorticoid deficiency during the first weeks of life. The largest numbers of cases have been described in Iranian Jews, who carried concomitantly two homozygous missense mutations (R181W and V386A). In a few cases with presumed aldosterone synthase deficiency no mutations in CYP11B2 gene have been identified. We describe a molecular and endocrine evaluation of seven cases of congenital hyperreninemic hypoaldosteronism in Israel. PATIENTS/METHODS: Two of the six Jewish patients are of Iranian origin. The parents of five other patients originated from Yemen, Syria and Morocco. One patient is a Muslim-Arab. CYP11B2's exons, exon-intron boundaries and promoter region were sequenced by multiple PCR amplifications. Gene size determination was performed either by long-range PCR or by Southern blot analysis. RESULTS: Only two patients (Iranian Jews) carried a known homozygous R181W, V386A mutations, other two were compound heterozygotes for either the R181W or V386A and one additional novel amino acid substitution (A319V or D335G), and one patient was found to be a carrier of the two novel variations (A319V and D335G). We could not find a molecular defect in 2 patients: one was a carrier of the D335G mutation and the other had no detectable molecular change in the coding and promoter regions. CONCLUSION: The genetic and molecular basis of congenital hyperreninemic hypoaldosteronism is more heterogeneous than previously described. The significance of amino acid substitutions identified in this study remains to be determined. 相似文献
18.
Devries IL Hampton-Smith RJ Mulvihill MM Alverdi V Peet DJ Komives EA 《FEBS letters》2010,584(23):4725-1965
The factor inhibiting HIF-1 (FIH-1) hydroxylates many ankyrin repeat-containing proteins including IκBα. It is widely speculated that hydroxylation of IκBα has functional consequences, but the effects of hydroxylation have not been demonstrated. We prepared hydroxylated IκBα and compared it to the unhydroxylated protein. Urea denaturation and amide H/D exchange experiments showed no change in the “foldedness” upon hydroxylation. Surface plasmon resonance measurements of binding to NFκB showed no difference in the NFκB binding kinetics or thermodynamics. Ubiquitin-independent proteasomal degradation experiments showed no difference in the half-life of the protein. Thus, it appears that hydroxylation of IκBα by FIH-1 is inconsequential, at least for the functions we could assay in vitro.
Structured summary
MINT-8051494: NF-kappa-B p65 (uniprotkb:Q04207) physically interacts (MI:0915) with NF-kappa-B p50 (uniprotkb:P25799) and I-kappa-B alpha (uniprotkb:O15111) by surface plasmon resonance (MI:0107) 相似文献19.
20.
Simon van Mourik Aalt DJ van Dijk Maarten de Gee Richard GH Immink Kerstin Kaufmann Gerco C Angenent Roeland CHJ van Ham Jaap Molenaar 《BMC systems biology》2010,4(1):101