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Biomedical subjects

L F van Zutphen

Publications and source records attributed to L F van Zutphen.

At least 37 records · Page 2Linked to original sources
PubMed1993

Toxicity testing and genetic quality control.

The genetic background of animals plays a major role in the outcome of toxicity tests. The use animals with a defined and standardized genetic variation as opposed to animals from an outbred strain may improve the quality of the tests and may reduce the numbers of animals to be used. In order to achieve this, animals from distantly related inbred strain (and their F1 hybrids) should be matched up in test and control groups (block design). The genetic distance between strains can be estimated by comparing the genetic profiles of strains which have been characterized for a set of monogenic marker genes. The establishment of the genetic strain profiles is also necessary when selecting the marker genes which are to be used for the genetic quality control of inbred strains. DNA markers, in particular the highly polymorphic SSLP's (microsatellites) are the most appropriate ones for this purpose.

Animals↗
PubMed1991

Segregation of genes from donor strain during the production of recombinant congenic strains.

Recombinant congenic strains (RCS) constitute a set of inbred strains which are designed to dissect the genetic control of multigenic traits, such as tumour susceptibility or disease resistance. Each RCS contains a small fraction of the genome of a common donor strain, while the majority of genes stem from a common background strain. We tested at two stages of the inbreeding process in 20 RCS, derived from BALB/cHeA and STS/A, to see whether alleles from the STS/A donor strain are distributed over the RCS in a ratio as would theoretically be expected. Four marker genes (Pep-3; Pgm-1; Gpi-1 and Es-3) located at 4 different chromosomes were selected and the allelic distribution was tested after 3-4 and after 12 generations of inbreeding. The data obtained do not significantly deviate from the expected pattern, thus supporting the validity of the concept of RCS.

Alleles↗
PubMed1991

Genetic variation within and between lines of diabetes-prone and non-diabetes-prone BB rats; allele distribution of 8 protein markers.

Twenty-four inbred and 2 outbred lines of the BB rat have been genetically characterized by establishing the allele distribution of 8 monogenic protein markers. The marker genes are: plasma alkaline phosphatase-1 (Alp-1), catalase-1 (Cs-1), carboxylesterases (Es-1, Es-2, Es-14), glyoxalase I (Glo-1), group specific component (Gc), and haemoglobin-beta-chain (Hbb). At least 3 linkage groups are represented by this set of markers. Genetic variation was found both within and between lines. Within-line variation was observed in 4 lines, including the 2 outbred lines. The other 22 lines could be subdivided into 4 groups, each representing a unique allele distribution pattern.

Alleles↗
PubMed1987

Genetics of a tissue esterase polymorphism (Est-6) in the rabbit (Oryctolagus cuniculus).

Genetic analysis of a polymorphic tissue esterase revealed a new locus (Est-6) with two alleles (Est-6a and Est-6b) on linkage group VI of the rabbit. Est-6 is closely linked to the Est-1,2,4 cluster. Esterase of Est-6 is found in many organs, particularly in liver and small intestine, but not in erythrocytes and serum. Est-6 esterase hydrolyzes alpha-naphthyl acetate and butyrate, naphthol AS-D acetate, indoxyl acetate, and butyrate as well as 5-bromoindoxyl acetate, N-acetyl-L-alanine-alpha-naphthyl ester but not 4-methylumbelliferyl acetate and fluorescein diacetate. The enzyme is inhibited by bis-p-nitrophenyl phosphate and eserine but not by p-chloromercuribenzoate. It was classified as a carboxylesterase (EC 3.1.1.1). Based on chromosomal localization, tissue distribution, substrate specificity, inhibitor sensitivity, and range of pI's, rabbit Est-6 is assumed to be homologous with mouse Es-7.

Alleles↗
PubMed1986

[Laboratory animals and animal experiments].

The historical development of the use of laboratory animals runs broadly parallel with the development of western human medicine. From the latter half of the nineteenth century, after the first anaesthetics were discovered, the number of animals used for experiments showed a particularly marked increase. A number of causes of these developments are discussed. From the latter half of the twentieth century, experimental animals themselves have become a subject of investigation. The discipline of laboratory animal science is then developed. Laboratory animal science increases the reproducibility of experimental studies and contributes to the welfare of laboratory animals. An important recent development was started in teaching laboratory animal science when the Laboratory Animal Order promulgated on May 31, 1985, became operative. In this Order, the training requirements are stated, which have to be met by those taking part in animal experiments (investigators, animal technicians, experts in laboratory animal science). A particular training in laboratory animal science is made compulsory on each of these categories. The Department of Laboratory Animal Science in Utrecht has national terms of reference for university education in this field. The contents of this education is briefly discussed. Finally, a number of problems are reviewed, which are associated with testing the ethical aspects of animal experiments.

Animal Testing Alternatives↗
PubMed1985

Assignment of Lap-1 to linkage group I of the rat (Rattus norvegicus).

Genetic analysis of backcross progeny from previously characterized rat inbred strains revealed that the biochemical marker Lap-1 is localized in linkage group I (LG I). Lap-1 codes for leucine arylaminopeptidase (EC 3.4.11). The distances of Lap-1 to c, RT6, and Hbb, based on recombination frequencies, are 3.1 +/- 1.5, 8.3 +/- 4.0, and 11.4 +/- 2.8 cM, respectively. Acon-1 codes for aconitase (EC 4.2.1.3). The calculated distances of Acon-1 to c and Hbb are 30.1 +/- 5.0 and 36.1 +/- 5.3 cM, respectively. This suggests that Acon-1 is also in LG I, but the observed high frequency of double crossovers requires further confirmation of this linkage. Ahd-2, Es-6, and Gdc-1 are linked neither to markers of LG I nor to one another.

Aconitate Hydratase↗
PubMed1983

Genetics of two tissue esterase polymorphisms (Est-4 and Est-5) in the rabbit.

Two polymorphic esterase systems were found after electrophoresis of rabbit tissue homogenates. Each of these systems is controlled by an autosomal locus with two alleles. Est-4 determines the absence (Est-4a) or presence (Est-4b) of two bands of esterase activity with intermediate anodcal mobility and broad substrate specificity. This polymorphism was found to be present in liver, small intestine, and spleen but not in kidney, heart, and testis. Est-5 is coding for cathodally migrating esterases which differ in mobility (Est-5a and Est-5b). This polymorphism was found only in kidney and testis homogenates. Est-5 esterases are more active against alpha-naphthyl acetate than against beta-naphthyl acetate and have no activity against alpha-naphthyl butyrate. Linkage analysis indicated that Est-4 is localized on rabbit LG VI as part of a cluster of esterase loci, whereas Est-5 segregates independently, Rabbits from two inbred and nine partly inbred strains were tested for these polymorphisms.

Alleles↗
PubMed1983

Separation of beta-D-galactosidases in rabbit tissues: genetics of neutral beta-D-galactosidase.

Three different types of beta-D-galactosidase (EC 3.2.1.23) could be distinguished in rabbit tissues using electrophoretic procedures. (1) Acid beta-D-galactosidase with a low mobility and maximal activity at pH 3-5 was found in the particulate fraction of various tissue homogenates. This enzyme hydrolyzed 4-methylumbelliferyl-D-galactoside, but no activity against other glycoside substrates could be demonstrated. The enzyme was inhibited by galactono-(1 leads to 4)-lactone. (2) Lactose-hydrolyzing beta-D-galactosidase with an intermediate mobility was found only in juvenile small intestine. Most of the activity was found in the particulate fraction of the cell. The enzyme hydrolyzed several other synthetic glycoside substrates besides lactose. It was most active at pH 5-6 and strongly inhibited by glucono-(1 leads to 5)-lactone but not much affected by galactono-(1 leads to 4)-lactone. (3) Neutral beta-D-galactosidase with a fast mobility and maximal activity at pH 6-8 was found in the soluble fraction of homogenates from liver, kidney, and small intestine. This enzyme also showed a broad substrate specificity; it possessed activity against aryl-beta-D-glucoside, -fucoside, and -galactoside substrates but not against lactose. The enzyme was strongly inhibited by glucono-(1 leads to 5)-lactone and (less) by galactone-(1 leads to 4)-lactone. Neutral beta-D-galactosidase and neutral beta-D-glucosidase (EC 3.2.1.21) are probably identical enzymes in the rabbit. Individual variation, in both electrophoretic mobility and activity, was found for neutral beta-D-galactosidase. Genetic analysis of the electrophoretic variants revealed that two alleles at an autosomal locus are responsible for this variation.

Animals↗
PubMed1981

Biochemical polymorphism in the rat: genetics of three electrophoretic variants and characterization of inbred strains.

Nine inbred strains of the rat (Rattus norvegicus) were screened for differences in electrophoretically detectable proteins. Interstrain variation was observed for 7 of 26 proteins. Three of these variants have not been described previously: leucine aminopeptidase (Lap-1), major urinary protein (Mup-1), and seminal vesicle protein (Svp-2). Genetic analysis revealed two autosomal alleles for each of these polymorphisms. The loci Lap=1, Mup-1, and Svp-2 are linked neither to one another nor to the previously described Svp-1 and Es-4 loci. Each of the nine strains can be identified now by a specific set of monogenic markers.

Animals↗
PubMed1981

Genetic and physiological aspects of cholesterol accumulation in hyperresponding and hyporesponding rabbits.

After a 5 week period of feeding a cholesterol-rich diet to rabbits, hyperresponders with high plasma cholesterol levels and hyporesponders with low plasma cholesterol levels could be distinguished from normal responders. The response was found to be correlated with the esterase genotype at the Est-2 locus. The increase in total body cholesterol was higher in hyper-than in hyporesponders. In both groups most of the accumulated dietary cholesterol was found in plasma and liver. Adrenal weight and plasma corticosterone levels were more increased in hyper- than in hyporesponders. The cholesterol-rich diet resulted in an augmentation of liver lipase and lipoprotein lipase activities. These lipolytic activities were more increased in hyper- than in the hyporesponders.

Adrenal Glands↗
PubMed1979

Chromosomal homology of rabbit (Oryctolagus cuniculus) linkage group VI with rodent species.

Homologous portions of linkage group (LG) VI in the rabbit Oryctolagus cuniculus, chromosome 8 in Mus musculus, and LG V of Rattus norvegicus have been observed. These linkage groups in Oryctolagus and Mus contain the extension locus (e), where recessive alleles are known in many species. Preliminary linkage data have added new loci to linkage group VI of the rabbit, revised the order and map distances on the linkage map, and by comparison with rodent species have strengthened the homology of LG VI in the rabbit with chromosome 8 of the mouse and with LG V of the rat. LG VI now contains five loci with the following order and intervening map distances: Es-1, Es-2 complex--6.3 +/- 2.1 cM--Est-1, Est-2 complex--18.5 +/- 3.7 cM--e.

Animals↗
PubMed1977

Serum esterase genetics in rabbits. IV. The prealbumin and beta-globulin systems.

Discontinuous starch gel electrophoresis revealed a fourth allele of rabbit pre-albumin serum esterase at locus Est-2. This allele is designated Est-2f and appears to be silent. In addition to the prealbumin serum esterases, another serum esterase system was studied in rabbits. This system is localized in the beta-globulin region. Genetic analysis indicated that one locus with two codominant alleles controls the variation in this region. Linkage of this system with Est-1 and Est-2 of the prealbumin serum esterases was demonstrated. Comparison of the arrangement of these esterase loci on linkage group VI with the esterase loci on chromosome 8 of the mouse gives additional support for the theory of evolutionary conservation of chromosomal segments coding for mammalian esterases.

Alleles↗
PubMed1975

Serum esterase genetics in rabbits. III. A third allele on the Est-2 locus.

A fast-migrating F' zone of the prealbumin serum esterase system of rabbits is demonstrated in low frequency in the breed Vienna White (stock Cpb:VW). Evidence is given that this zone is controlled by a third allele of the Est-2 locus. The zymotypic expression of this allele (Est-2-F') shows codominance in combination with the Est-2-F allele and complete dominance in combination with the Est-2-F' allele. In contradistinction to the F zones of the Est-2-F allele, the F' zone possesses no atropinesterase activity.

Alleles↗
PubMedDate not supplied

Developments on the implementation of the Three Rs in research and education.

More than 40 years ago, Russell and Burch published their views on the implementation of the 'Three Rs' in animal experimentation. Since then, much has been achieved in this area. Recently, the European Science Foundation (ESF) has made a further step forward. In a position paper on the use of animals, ESF has formulated what it sees as prerequisites for the humane use of animals in research, testing and education. In this paper, we briefly report on these ESF guidelines. Also, an overview is presented on European legislative regulations for the (ethical) review of research protocols and for the education and training of persons involved in animal experiments. The great diversity between countries is illustrated with some examples and the need for harmonization is emphasised. The paper ends by highlighting the special role that editorial boards of journals can play in the further implementation of the Three Rs.

Animal Testing Alternatives↗
PubMedDate not supplied

Strain differences in the prealbumin serum esterases of JAX rabbits.

The serum prealbumin esterase phenotypes were determined for 431 adult rabbits representing the majority of the breeding stock of the genetically defined JAX rabbits. Uniform phenotypes were observed in 8 of the 15 strains where adequate samples were obtained. In all of the phenotypes where uniformity was observed, the Est-2F gene was lacking. Also, all 431 rabbits lacked the Est-3D allele commonly observed in Europe. A sex difference was seen in the f' zone, which was darker in females than in males when the staining process was twice the normal length of time.

Animals↗