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L F van Zutphen

Publications and source records attributed to L F van Zutphen.

At least 19 recordsLinked to original sources
PubMed2001

Genetic and correlation analysis of hepatic copper content in the rat.

Thirty recombinant inbred (RI) strains derived from the spontaneous hypertensive rat (SHR/OlaIpcv) and the Brown Norway (BN-Lx/Cub) progenitors were used to search for quantitative trait loci (QTLs) that are responsible for differences in liver copper between these two strains. The heritability of liver copper concentration (expressed as microg/g liver wet wt and microg/g liver dry wt) and liver copper store (microg/whole liver) was estimated to be 57, 57, and 46%, respectively. In a total genome scan of the RI strains, involving over 600 genetic markers, suggestive association was found between liver copper store (microg/whole liver) and the D16Wox9 marker on chromosome 16 (lod score = 2.8), and between liver copper concentration (microg/g dry wt) and the D10Cebrp1016s2 marker on chromosome 10 (lod score = 3.0). These putative QTLs are responsible for nearly 34 and 40% of the additive genetic variability for liver copper store and concentration, respectively.

Animals↗
PubMed2001

Genetic analysis and mapping of biochemical markers in an F2 intercross of two inbred strains of the rabbit (Oryctolagus cuniculus).

A total of 40 biochemical and four immunological markers found to be polymorphic in the rabbit in previous studies were screened in the AX/JU and IIIVO/JU inbred strains. Although the strains are considered unrelated, only eight (biochemical) markers werefound to be polymorphic between the two strains. These eight markers were analyzed in an F2 intercross population. Linkage was found for Est-5 and C on chromosome 1 and for Es-1, Est-2, Est-4, Est-6 and HP on linkage group VI. Two polymorphic markers, Es-3 and Mhr-1 could not be linked to any of the other markers.

Animals↗
PubMed2001

Mapping of rabbit chromosome 1 markers generated from a microsatellite-enriched chromosome-specific library.

A genomic DNA library was produced from flow-sorted rabbit chromosome 1 and enriched for fragments containing CA-repeats. Clones containing CA-repeats were identified and primers for amplification of the microsatellite were developed after sequencing the clone. The degree of polymorphism was tested in rabbits from different breeds. This approach identified 12 microsatellite markers which could be used for studying linkage relationships in the progeny of an F(2)-intercross: (AX/JUxIIIVO/JU) F(2), and two backcrosses: (OS/JxX/J)X/J and (WH/JxX/J)X/J. Seven of these markers were mapped on chromosome 1.

Animals↗
PubMed2001

Congenic BB.SHR rat provides evidence for effects of a chromosome 4 segment (D4Mit6-Npy approximately 1 cm) on total serum and lipoprotein lipid concentration and composition after feeding a high-fat, high-cholesterol diet.

Congenic BB.SHR (previously referred to as BB.LL) rats were generated by transferring the segment of chromosome 4 flanked by the D4Mit6 and Spr loci from the spontaneously hypertensive rat (SHR/Mol) onto the genetic background of the diabetes-prone BB/OK rat. In this study, the influence of the above-mentioned region of chromosome 4 on triglyceride, cholesterol, and phospholipid phenotypes after a high-fat, high-cholesterol diet was examined by comparison of BB.SHR congenic rats with BB/OK rats. BB/OK and BB.SHR had comparable concentrations of basal and postdietary serum insulin, as well as of basal total serum triglycerides and had an identical body weight and food intake at the beginning of the test period. However, after 4 weeks on the test diet, BB.SHR rats were significantly heavier than BB/OK rats and had significantly higher food intake and lower total serum triglyceride concentrations. The basal serum leptin level was significantly lower, but postdietary serum leptin concentration did not show a significant difference between the 2 strains. Furthermore, significantly higher basal total serum cholesterol and phospholipid levels were observed in BB.SHR rats, but this difference disappeared after feeding the high-fat, high-cholesterol diet. Postdietary high-density lipoprotein (HDL)(2) cholesterol and phospholipid levels were significantly elevated in BB.SHR rats when compared with BB/OK rats. The 2 strains also differed slightly, but significantly, with respect to the other HDL phospholipid concentrations. In addition to previously described differences between BB/OK and BB.SHR rats, the results of this study clearly show the impact of genes, lying within the transferred segment, on serum lipid phenotypes after high-fat, high-cholesterol diet.

Alleles↗
PubMed2001

Use of score sheets for welfare assessment of transgenic mice.

The use of transgenic mice has increased dramatically in recent years and continues to increase further. However, because transgenesis may alter a balanced genotype and produce unpredictable effects, careful monitoring of health and welfare of the transgenic animal is advised. The present study assessed the feasibility of the use of score sheets for monitoring transgenic mice, as part of daily routine, in a transgenic unit. The score sheets used were based on parameters which are sensitive and easy to determine. The score sheets were used by two animal technicians and a thorough evaluation showed that the score sheets, as described in this paper, are useful for routine monitoring in a transgenic unit and may result in the early detection of animal welfare problems. However, notwithstanding the limited number of parameters included and the restricted age-span covered by the screening, the monitoring system was considered to be time consuming. Large-scale implementation of such a scoring system during the first weeks of life would increase daily care time by at least 15-20 min for an average litter of 4-6 pups. Nevertheless, the use of score sheets seems to be a prerequisite for monitoring the animal's welfare in the course of producing transgenic lines.

Aging↗
PubMed1999

Complete homology maps of the rabbit (Oryctolagus cuniculus) and human by reciprocal chromosome painting.

Fluorescence in situ hybridization (FISH) was used to construct a homology map to analyse the extent of evolutionary conservation of chromosome segments between human and rabbit (Oryctolagus cuniculus, 2n = 44). Chromosome-specific probes were established by bivariate fluorescence activated flow sorting followed by degenerate oligonucleotide-primed PCR (DOP-PCR). Painting of rabbit probes to human chromosomes and vice versa allowed a detailed analysis of the homology between these species. All rabbit chromosome paints, except for the Y paint, hybridized to human chromosomes. All human chromosome paints, except for the Y paint, hybridized to rabbit chromosomes. The results obtained revealed extensive genome conservation between the two species. Rabbit chromosomes 12, 19 and X were found to be completely homologous to human chromosomes 6, 17 and X, respectively. All other human chromosomes were homologous to two or sometimes three rabbit chromosomes. Many conserved chromosome segments found previously in other mammals (e.g. cat, pig, cattle, Indian muntjac) were also found to be conserved in rabbit chromosomes.

Animals↗
PubMed1999

HXB/Ipcv and BXH/Cub recombinant inbred strains of the rat: strain distribution patterns of 632 alleles.

The HXB/Ipcv and BXH/Cub sets of recombinant inbred (RI) strains were derived from the spontaneously hypertensive rats (SHR/OlaIpcv) and normotensive Brown Norway (BN-Lx/Cub) rats. The RI strains were produced as a model system for genetic and correlation analysis of spontaneous hypertension and other risk factors of cardiovascular disease such as insulin resistance and dyslipidemia. The RI strains were phenotyped in multiple hemodynamic and metabolic traits. In the current study, we describe strain distribution patterns of 632 genetic markers.

Alleles↗
PubMed1998

Genetic analysis of dystrophic cardiac calcification in DBA/2 mice.

A DBA/2 x D2B6F1 backcross was produced in order to study the genetic background of pathological soft tissue calcification in the mouse. Calcification was assessed in the myocardium, kidney and tongue. Significant co-segregation was found with the genotype of microsatellite markers on the proximal end of Chromosome 7. This region contains a candidate gene, Hrc, coding for the histidine-rich calcium binding protein in the sarcoplasmatic reticulum. The results support the hypothesis that the gene previously reported to be responsible for DCC (dystrophic cardiac calcification) in C3H mice (1) causes generalized soft tissue calcification in DBA/2 mice.

Animals↗
PubMed1998

A genetic and correlation analysis of liver cholesterol concentration in rat recombinant inbred strains fed a high cholesterol diet.

Liver cholesterol concentration in rats fed a high cholesterol diet, is under genetic control which is supported by significant differences observed among inbred strains. For instance, the Brown Norway (BN-Lx/Cub) rat developed a twofold higher liver cholesterol concentration than the spontaneously hypertensive rat (SHR/Ola). In the current study, we used 30 recombinant inbred (RI) strains, derived from BN-Lx and SHR progenitors, to locate quantitative trait loci (QTL) that are responsible for differences in liver cholesterol concentrations between the BN-Lx and SHR strains. The heritability of liver cholesterol was estimated to be 0.55 and a significant association was detected between concentration of liver cholesterol and the D10Cebrp1016s2 marker on chromosome 10 (lod score = 3.3); this putative QTL was responsible for nearly 64% of additive genetic variability and thus represents a major genetic determinant of liver cholesterol concentration. Liver cholesterol concentrations significantly correlated with intermediate density lipoprotein (IDL) cholesterol levels.

Animals↗
PubMed1998

The influence of transportation stress on selected nutritional parameters to establish the necessary minimum period for adaptation in rat feeding studies.

The optimal length of the adaptation period after transportation of rats, to be used in nutritional studies, was investigated in this study. After intracontinental transportation of rats by car and by air to and from the laboratory for a total period of 15 h, measurements were carried out for a period of 3 weeks after transport. Control and transported animals were housed in the same laboratory before and after transportation. During transport the animals had access to food and water. As blood collection could also cause stress, a factorial design was carried out with transport and blood collection as main factors. Transport or blood collection did not cause significant effects on the following parameters: body weight, growth, clinical observation, and blood enzyme activities of LDH and ASAT. Water intake was significantly increased after transport. Food intake did not show consistent effects after transport or blood collection. Unexpectedly, blood corticosterone levels were significantly lower in the transported animals at day 1 after transport. After 3 days these levels were back to normal. Blood glucose, blood free fatty acids and blood urea nitrogen concentrations were incidentally decreased, whereas total cholesterol levels showed an incidental rise in the transported rats. The open-field behaviour test revealed no clear-cut results concerning the effects of transport or blood collection on faeces production, rearing and ambulation. Our results indicate that after intracontinental transport, an adaptation period of 3 days appears to be sufficient for rats to be used in nutritional studies.

Adaptation, Physiological↗
PubMed1997

Mapping genes controlling hematocrit in the spontaneously hypertensive rat.

The genes that determine the baseline hematocrit level in humans and experimental animals are unknown. The spontaneously hypertensive rat (SHR), the most widely used animal model of human essential hypertension, exhibits an increased hematocrit when compared with the normotensive Brown Norway (BN-Lx) strain (0.54 +/- 0.02 vs. 0.44 +/- 0.02, p < 0.01). Distribution of hematocrit values among recombinant inbred (RI) strains derived from SHR and BN-Lx progenitors was continuous, which suggests a polygenic mode of inheritance. The narrow heritability of the hematocrit was estimated to be 0.32. The Eno2 marker on Chromosome (Chr) 4 showed the strongest association (p < 0.0001) with the observed variability of hematocrit among RI strains. The erythropoietin (Epo) gene, originally reported to be syntenic with Eno2, has been mapped to Chr 12, thus excluding it as a potential candidate gene for the increased hematocrit in the SHR. The current linkage data extend homologies between rat, mouse, and human chromosomes.

Animals↗
PubMed1996

Strain-specific response to hypercholesterolaemic diets in the rat.

The cholesterolaemic effect of 2 hypercholesterolaemic diets was tested in 12 rat inbred strains. Diet I is a commercial diet supplemented with 2.0% (w/w) cholesterol and 5.0% (w/w) olive oil; diet II is identical to diet I with addition of 0.5% (w/w) sodium cholate. Strains with the highest plasma cholesterol response after diet I (BN and LEW) also had the highest cholesterol response after diet II (hyperresponders, mean response > 3.5 mmol/l). In the strains DA, SHR, BC, WAG, LOU, PVG and BUF the strain mean cholesterol response remained below 1.3 mmol/l after both diets (hyporesponders). Strains F344 and OM had an intermediate cholesterol response after both diets (normoresponders, mean response between 1.3 and 3.5 mmol/l). Only in the strains LOU, PVG and SHR there appeared to be a significant higher cholesterol response after diet II when compared with the cholesterol response after diet I. In the strain WKY this difference was of a borderline significance (P = 0.052) and this strain turned from a normoresponder after diet I into a hyperresponder after diet II. Liver cholesterol levels as measured after feeding diet II for two weeks also appeared to be strain-specific. No correlation was found between the plasma cholesterol response after diet II and the liver cholesterol levels. Changes in plasma phospholipid and triglyceride levels have been measured for both diet I and diet II. For group means a correlation between the cholesterol response and the change in phospholipid levels was found (r = 0.86 for diet I, P < 0.001 and r = 0.76 for diet II, P < 0.01). No such correlation was found for triglyceride levels.

Animals↗
PubMed1994

Immunogenicity testing of diphtheria and tetanus vaccines by using isogenic mice with possible implications for potency testing.

The antitoxin response of isogenic mice (inbred strains and F1 hybrids), immunized with diphtheria and tetanus reference vaccines, was compared with the response of animals from an NIH outbred stock. The variance in antitoxin response was smaller within the groups of isogenic mice than within the group of mice from the outbred strain. The case for estimating the potency of diphtheria and tetanus vaccines by using isogenic mice is discussed. It is concluded that the general introduction of one common inbred strain or F1 hybrid selected on the basis of sensitivity would increase the comparability of data between laboratories and would enable an estimated reduction in the use of animals of about 35% or an improvement in the precision of the estimate of potency.

Animals↗
PubMed1994

Strain specific behavioural response to environmental enrichment in the mouse.

The influence of environmental enrichment on the behaviour of the mouse has been studied in two inbred strains (C57BL and BALB/c). Male mice of each of the two strains were subjected to behavioural tests after being housed for two months either under standard housing conditions or in an enriched environment. The results of the behavioural test indicated that the C57BL mice housed in the enriched environment were more reactive and alert compared to mice housed in the standard environment. In the BALB/c mice results may be interpreted as if enriched environments lead to an increased level of anxiety. It is concluded that environmental enrichment has a strain specific effect on the behaviour of mice.

Animals↗