Co-segregation of intermale aggression with the pseudoautosomal region of the Y chromosome in mice.

The sexual dimorphism of aggression has led to a search for its Y chromosomal correlates. We have previously confirmed that initiation of attack behavior against a conspecific male is Y-dependent in two strains of laboratory mice (NZB and CBA/H). We provide evidence that the non-pseudoautosomal region of the Y is not involved and that only the pseudoautosomal region of the Y is correlated with initiation of attack behavior. The autosomal correlates also contribute to this behavior in an additive or interactive manner with the pseudoautosomal correlates.

Linkage between brain serotonin concentration and the sex-specific part of the Y-chromosome in mice.

The implication of the sex-specific part of the Y-chromosome (YS-SP) on brain serotonin (5-HT) level was investigated using congenic strains for this chromosomal region. The 5-HT level, which was higher in the NZB than in the CBA/H strain of mice, was depleted by the transfer of the YS-SP from NZB on CBA/H whereas the transfer of the YS-SP from CBA/H on NZB had no effect. The variations of 5-HT levels were not correlated with plasma testosterone concentration which is also dependent of the YS-SP.

Hippocampal mossy fiber changes in mice transgenic for the human copper-zinc superoxide dismutase gene.

The copper-zinc superoxide dismutase (SOD-1) gene, located on chromosome 21 and triplicated in Down's syndrome (DS), is suspected to be involved in the neuropathology observed in Alzheimer's disease (AD), DS and physiological aging. In order to explore the effect of an overproduction of SOD-1 in the mouse hippocampus, we investigated the Timm-stained mossy fiber (MF) innervation in the hippocampus of transgenic mice for the human SOD-1 gene (hSOD-1 mice). The results showed a decrease of the MF projection area in the hSOD-1 mice overexpressing the SOD-1 protein. These findings suggest that free radicals could play a role in this particular synaptic loss.

Influence of castration and brain GABA levels in three strains of mice on aggression towards lactating intruders.

This study examined the relationship among aggression towards lactating intruders, castration and brain GABA levels in three strains of mice (C57, C3H and CBA). Both C57 and C3H (but not CBA) animals showed reduced attack latencies following castration. C57 mice showed the highest intensity of this behavior and the response was almost absent in the CBA strain. Considerable strain differences in brain GABA levels were observed. In particular the most aggressive C57 castrates had significantly higher levels of GABA in the hypothalamus, the olfactory bulbs and the amygdala. Such changes are not recorded in C3H or CBA strains of mice, which are both characterized by low levels of baseline aggression towards lactating intruders.

Induction of heterotopic bone marrow formation in osteopetrotic rats by allogeneic decalcified bone matrix.

Contrary to theoretical expectations in osteopetrotic mutants heterotopic bone marrow formation was closely associated with osteogenesis, what is not observed in the orthotopic skeletal bones in these animals.

Heterotopically induced osteogenesis in osteopetrotic rat mutants. A preliminary report.

Heterotopic osteogenesis was induced in three groups of Fatty Orl-op strain of rats, i.e., osteopetrotic (op/op) mutants, op/op mutants cured by previous transplants of normal bone marrow, and phenotypically normal littermates. Allogenic decalcified bone matrix was used as inductor. The osteopetrotic mutants from heterotopic ossicles containing bone and bone marrow under the influence of inductor. After four weeks the signs of remodelling processes of induced bone tissue are observed: osteoclasts are found in the Howship lacunae, and bone marrow is formed in the spaces adjacent to the bone trabeculae. The induced bone marrow contains megakaryocytes, cells of the erythropoietic and granulopoietic lines as well as some infiltrating lymphocytes. The important finding is that the amount and the histological structure of bone tissue and bone marrow induced heterotopically in the osteopetrotic animals were similar to that observed in both control groups. It is concluded that 1) osteopetrotic mutants have the same potency to form heterotopic bone tissue under the influence of inductor as the control animals, and 2) remodelling processes in four-week-old, induced ossicles are normal and differ in this respect from defective rebuilding of the orthotopic bones of op/op hosts.

Mandible shape analysis in Y-congenic strains of mice.

In order to test for the presence of genes influencing morphology on the Y-chromosome of mice, a canonical discriminant analysis of variation in mandible shape was conducted in 4 inbred strains of mice and 4 Y-chromosome congenic partners. Genetic background-dependent differences were observed, as well as a small sex variation in some strains, but it was impossible to detect any difference related to the between-strain exchange of the Y-chromosome.

Early and transient osteopetrosis in microphthalmic MIB-rats.

Microphtalmic blanc mutation (mib/mib) displays a very mild form of osteopetrosis in rats. The autosomal recessive mib mutation shows pleiotropic expressions in homozygotes. Microphtalmia, absence of eye and skin pigmentation, retardation in the tooth eruption were observed in the mutants. Most bone abnormalities occurred in newborns. An increased radiological opacity of long bones, persistence of primitive bone in medullary cavities, reduced number of poorly differentiated osteoclasts in mandibulae, reduced number of mononuclear peritoneal cells as well as reduced number of mononuclear osteoclast precursors in peritoneal cell population were found. In 3 weeks old and in adult mutants, both bone structure and the number of mandible osteoclasts appear normal, but the number of blood monocytes, peritoneal cells and mononuclear osteoclast precursors in peritoneal cell population remain significantly lower than in the healthy littermates. These observations indicate that the early failure of osteoclast differentiation and maturation is transient in the mib/mib form of osteopetrosis.

Comparative evaluation of the immune status of congenitally athymic and euthymic rat strains bred and maintained at different institutes: 1. Euthymic rats.

We performed a comparative evaluation of the immune status, focused on the T-cell system, of euthymic rat strains in which the nude mutation had been introduced. From 10 institutes, we sampled 12 groups of euthymic rats at ages of 1 1/2-2 months and 1/2 year. We analyzed weight of body, spleen and thymus; antibody response and delayed-type hypersensitivity response to ovalbumin immunization; and (immuno)histopathology of spleen, lymph nodes, and lymphoid tissue along the gastrointestinal tract. In the spleen morphometric analysis was done of the periarteriolar lymphocyte sheath (using the antibody R73 recognizing the alpha beta-T-cell receptor) and of the red pulp (using the antibody ED2 recognizing red pulp macrophages). For almost all parameters tested, statistically significant differences between the groups (origin of the animals) were observed. A cluster analysis on the basis of body weight, spleen weight, and morphometric data of spleen did not yield clusters with a different composition among animals from individual groups. Based on the antibody response to ovalbumin, clustering revealed groups of "fast-and-high", "slow-and-low", and "intermediate" responders. The various groups differed in location within these clusters, i.e. the speed and extent of the immune response depends on the background euthymic strain. Considering the microbiological status assessed by serology, a variation was found both in post-infection state at entrance in the study, and in primo-infection associated with a rise in antibody concentrations during the study. These states showed no negative effect on anti-ovalbumin reactivity. Rather, the response in primo-infection to Rat Corona Virus, Sendai Virus, and Pneumonia Virus of Mice was the highest in animals clustered as "fast-and high" responders to ovalbumin.

Comparative evaluation of the immune status of congenitally athymic and euthymic rat strains bred and maintained at different institutes: 2. Athymic rats.

We performed a comparative evaluation of the immune status, focused on the T-cell system, in congenitally athymic rat strains. From 11 institutes around the world, we sampled 15 groups of animals at ages of 1 1/2-2 months and 1/2 year. The analysis included weight of body and spleen; antibody response and delayed-type hypersensitivity response after immunization with ovalbumin; and (immuno)histology of spleen, lymph nodes and lymphoid tissue along the gastrointestinal tract. Morphometric analysis was done for alpha beta-T-cell receptor-bearing cells in spleen tissue as a measure of the periarteriolar lymphocyte sheath; it was also done for splenic red pulp using the antibody ED2 recognizing red pulp macrophages. For almost all variables analyzed, statistically significant differences between the groups were observed. The extent of alpha beta-T-cell receptor-bearing cells in the spleen increased with age. The functioning of these cells in immunological responses can be questioned, because an immune response to ovalbumin was invariably absent. But secondary follicles with germinal centers, reflecting T-cell-dependent B-cell reactivity, were observed in lymph nodes and Peyer's patches (up to 40% and 75%, respectively, depending on the group), with a higher prevalence in older animals. A cluster analysis on the basis of body and spleen weight and composition of spleen compartments did not yield clusters with a different profile in regard to the animals' group of origin. The data presented are useful when comparing studies performed with various athymic rat strains at different institutes.

[Models of genetic hypertension in the rat: recent trends]. / Les modèles d'hypertension génétique chez le rat: acquisitions récentes.

Six principal strains of rats have been selected to develop spontaneous or induced hypertension, the SHR (Okamoto) strain alone being widely used by experimenters. This is the case in France and it is to be desired that investigations are extended at two levels: introduction of new substrains; improvement and comparative genetic study of available strains. The Centre de Sélection et d'Elevage d'Animaux de Laboratoire is already engaged in that way, making every effort to promote the utilization of the newly obtained SHR SP subline as well as that of the SHR-fa subline which is in the process of being established.

Linkage of the hypodactyly and incisorless genes in the Norway rat.

The linkage of the hypodactyly (hd) and incisorless (ia) loci in linkage group II of the rat has been established. The data give 22 +/- 4 percent recombination. However, these markers failed to confirm the position of the brown gene (b) in the same linkage group.

[Cure of osteopetrosis by injection of allogenic bone marrow into "op" rats treated with cyclosporin A]. / Guérison de l'ostéopétrose par injection de moelle osseuse allogénique chez le rat "op" traité par la cyclosporine A.

The cure of osteopetrosis by allogenic bone marrow injection has been obtained in "op" mutant rat kept under cyclosporin A treatment. This immunosuppressive agent able to prevent the rejection of transplanted cells does not impair the propriety of these cells to restore the bone resorption process in this severe osteopetrotic form.

Identification of inbred strains of mice: II. Characterization of different substrains of the C3H strain.

Substrains of inbred C3H mice differ significantly in their genetic constitution with respect to biochemical markers, skin grafting, and skeletal variations. The presence of such discrepancies among substrains poses a problem when comparing conclusions based on experiments done in different substrains. Therefore, methods of controlling the genetic constitution are necessary and important to avoid these discrepancies.

Syp-3, a third polymorphic locus for mouse seminal vesicle proteins.

The B10.AKM/Sn congenic strain displays a particular phenotype of mouse seminal vesicle proteins representing the third polymorphic locus of this system. The Svp-3 symbol was assigned to this locus with two codominant alleles, Svp-3a found in the B10.AKM/Sn strain and Svp-3b expressed by all the other strains so far tested. The Svp-3 locus appears tightly linked to Svp-1 on chromosome 2.

Enzyme-histochemical changes in arteries of genetically hypertensive rats (SHR, SP-SHR).

To determine the effect of the duration and severity of hypertension on arterial wall metabolism 28 enzyme activities and several macromolecular complexes were histochemically studied in normotensive (WK), moderately (SHR) and strongly hypertensive (SP-SHR) rats at various ages. The results indicate that the abnormalities of 5' nucleotidase, acid esterase, cholinesterase and Alk.P. appeared in prehypertensive 4 w.old SHR. The posthypertensive changes, fluctuating in relation to the duration of hypertension, concerned: the pentose pathway, Krebs cycle and glycolosis -linked dehydrogenases; lysosomal enzymes; glycogen-phosphorylase and MAO; glycosaminoglycan and glycoprotein content. The structural and metabolic response presented several local and regional differences. The metabolic changes were greater in the aorta than in the caudal and femoral arteries. The comparison between SHR and SP-SHR indicates that the blood pressure (BP) at 170 mm Hg seems well tolerated during a long period of time. Severe lesions such as degeneration and failure of lipolytic activity in aortic smooth muscle cells (SMC), notable and early (8 mo.) in SP-SHR with 240 mm Hg were less intense and appeared later (13 mo.) in SHR with 190 mm Hg. The level of hypertension, rather than its duration, appears as a determining factor of posthypertensive vascular damage.

[Cure of osteopetrosis by allogenic bone marrow injection in the double mutant "osteopetrosi-athymic" rat]. / Guérison de l'ostéopétrose par injection de moélle osseuse allogénique chez le rat double-mutant "ostéopétrotique-athymique".

The cure of osteopetrosis by allogenic bone marrow injection has been obtained in homozygous rats for both mutations, osteopetrosis (op) and athymic nude (rnu). This new animal model will help in studying the eventual relationship between the bone resorption process and the immunological reconstitution.