Expression of Thy-1, H-2 and NS-4 cell surface antigens and tetanus toxin receptors in early postnatal and adult mouse cerebellum

The expression of several cell surface components (Thy-1, H-2 and NS-4 antigens and tetanus toxin receptors) was studied by indirect immunofluorescence in situ using histological sections and in vitro using freshly dissociated and cultured cells from mouse cerebellum. Thy-1 alloantigen is expressed in adult cerebellum predominantly in neuron-rich regions, i.e. molecular, Purkinje cell, and granular layers, however, it is not detectable at postnatal day 8. In cerebellar cultures of 6-day-old mice Thy-1 is absent from more than 99% of all cells when these are maintained as monolayers in vitro for up to 3 days. After 4 days in vitro some GFA protein-positive astrocytes and some fibronectin-positive fibroblast-like cells start to express Thy-1 antigen. After 14 days in vitro not all fibroblast-like cells and astrocytes are Thy-1 antigen-positive. Neurons with small cell bodies and oligodendrocytes never express Thy-1 at any stage examined. H-2 is not expressed sufficiently to be detectable in histological sections in early postnatal or adult cerebellum. In cerebellar cultures of 6-day-old mice H-2 becomes detectable on some fibroblast-like cells and some astrocytes after 7 days in culture. In histological sections of adult and early postnatal cerebellum NS-4 antigen and tetanus toxin receptors are expressed predominantly in neuron-rich regions. In the developing cerebellum both are expressed at higher levels on more mature granule cells. In cerebellar cultures NS-4 antigen and tetanus toxin receptors are expressed on neurons. Occasionally some astroglia can also show detectable levels of expression. NS-4 antigen is also present on some 04 antigen-positive oligodendrocytes, while tetanus toxin receptors are never detectable on these cells.     

T-cells specific for soluble recombinant oligodendrocyte-specific protein induce severe clinical experimental autoimmune encephalomyelitis in H-2(b) and H-2(s) mice

To investigate the immunogenicity and encephalitogenicity of oligodendrocyte-specific protein (OSP), recombinant soluble mouse OSP (smOSP) was produced from a synthetic gene engineered to lack the sequences coding for the hydrophobic transmembrane domains of the native molecule. SmOSP was immunogenic and encephalitogenic for SJL/J, C3H.SW and C57BL/6J mice, but not PL/J or BALB/c mice. SmOSP-specific T-cells from SJL/J, C3H.SW and C57BL/6J mice induced severe chronic clinical experimental autoimmune encephalomyelitis upon transfer. These findings indicate that autoimmune T-cell responses to OSP should be investigated in the context of multiple sclerosis.     

Characterization of isolated mouse cerebellar cell populations in vitro

The expression of several cell surface components (Thy-1, H-2 and NS-4 antigens and tetanus toxin receptors) was studied by indirect immunofluorescence in situ using histological sections and in vitro using freshly dissociated and cultured cells from mouse cerebellum. Thy-1 alloantigen is expressed in adult cerebellum predominantly in neuron-rich regions, i.e. molecular, Purkinje cell, and granular layers, however, it is not detectable at postnatal day 8. In cerebellar cultures of 6-day-old mice Thy-1 is absent from more than 99% of all cells when these are maintained as monolayers in vitro for up to 3 days. After 4 days in vitro some GFA protein-positive astrocytes and some fibronectin-positive fibroblast-like cells start to express Thy-1 antigen. After 14 days in vitro not all fibroblast-like cells and astrocytes are Thy-1 antigen-positive. Neurons with small cell bodies and oligodendrocytes never express Thy-1 at any stage examined. H-2 is not expressed sufficiently to be detectable in histological sections in early postnatal or adult cerebellum. In cerebellar cultures of 6-day-old mice H-2 becomes detectable on some fibroblast-like cells and some astrocytes after 7 days in culture. In histological sections of adult and early postnatal cerebellum NS-4 antigen and tetanus toxin receptors are expressed predominantly in neuron-rich regions. In the developing cerebellum both are expressed at higher levels on more mature granule cells. In cerebellar cultures NS-4 antigen and tetanus toxin receptors are expressed on neurons. Occasionally some astroglia can also show detectable levels of expression. NS-4 antigen is also present on some 04 antigen-positive oligodendrocytes, while tetanus toxin receptors are never detectable on these cells.     

Expression of selected antigens on the surface of cultured neural cells

Immunofluorescence, immunoradioautography and immunoabsorption were employed to evaluate surface expression of selected species specific and ‘nervous system specific’ determinants in various cultured neural cell lines. Three murine neural cell lines (A/J neuroblastoma, C3H/HeJ astrocytoma, C57B1/6J ependymoblastoma) and their various clones expressed surface H-2 antigenicity appropriate for the parent strain. No evidence was obtained for surface expression of S100 protein, 14-3-2 protein, myelin basic protein, Thy-1.1 ( C3H) or PC-1 antigens on assorted neural cell lines from mouse, rat and man.     

Neurospecific S-100 protein content in brains of different mouse strains

Total whole brain concentrations of S-100 protein and of its water-soluble fraction were determined in 11 inbred mouse straine: DBA/2J, AKR/J, CBA/Lac, C57BL/6J, C57BL/6J-Ay, C3H/He, C3H/f, DD, A/He, BALB/cLac, CC57BR/Mv, and in cerebral cortex, cerebellum and hippocampus in DBA/2J, AKR/J and CBA/Lac strains. Highly significant differences in the concentrations of the water-soluble S-100 protein were found between some strains. Slight differences were found in total S-100 protein content in whole brains between the strains (0.01 less that P less than 0.05). The DBA/2J mice had the highest brain S-100 protein content, and were characterized by a higher learning rate in shuttle-box as compared to CBA/Lac and AKR/J mice, who had a low content of this neurospecific protein.     

Production of antibodies to human factor viii in the ascitic fluid of C57BL/6J mice

A method is described for the production of a murine antiserum to human factor VIII, and the quantitation of factor VIII related antigen using this antiserum. C57BL/6J mice were injected intraperitoneally with a mixture of factor VIII and complete Freund's adjuvant. Ascitic fluid developed after repeated innoculations for seven to eight weeks, and was subsequently tapped. Using this antiserum, factor VIII related antigen was quantitated by immunoelectrophoresis and enzyme immunoassay. This method provides a simple and economical way of producing an antiserum to factor VIII, and may also be applicable to other proteins available in submilligram quantities.     

Cell-specific expression of the epm1 (cystatin B) gene in developing rat cerebellum

Cystatin B (cystB) is an anti-protease implicated in EPM1, a degenerative disease of the central nervous system. This work analyzes the pattern of expression of cystB in developing and adult cerebellum, identifying the cystB positive cells by double immune-fluorescence microscopy using specific cell markers. In primary glial cells, cystB is found in progenitor and differentiated oligodendrocytes as well as in astrocytes. In the cerebellum, only oligodendrocyte progenitors express cystB. In myelin-producing cells, cystB synthesis is strongly down-regulated and the protein is not detectable. Astrocytes and Bergmann glia express cystB at all the developmental stages analyzed both in the cell body and in the fibers. Most neurons of developing and adult rat cerebellum do not express detectable amounts of cystB, with the exception of the Purkinje cells and of some cells of the differentiated molecular layer. In human cerebellum, cystB is present in Purkinje cells and Bergmann glial fibers only. cystB is also found in the cortical neurons of the dentate gyrus of the hippocampus. In rat cerebellum, cystB forms a complex with a number of proteins, two of which are specific to the nervous system. The cellular co-localization of cystB and its partners in developing and adult cerebellum is also shown.     

Genetic variance contributes to naltrexone-induced inhibition of sucrose intake in inbred and outbred mouse strains

The study of genetic variance in opioid receptor antagonism of sucrose and other forms of sweet intake has been limited to reductions in sweet intake in mice that are opioid receptor-deficient or lacking either pre-pro-enkephalin or beta-endorphin. Marked genetic variance in inbred mouse strains has been observed for sucrose intake across a wide array of concentrations in terms of sensitivity, magnitude, percentages of kilocalories consumed as sucrose and compensatory chow intake. The present study examined potential genetic variance in systemic naltrexone's dose-dependent (0.01-5 mg/kg) and time-dependent (5-120 min) ability to decrease sucrose (10%) intake in eleven inbred (A/J, AKR/J, BALB/cJ, CBA/J, C3H/HeJ, C57BL/6J, C57BL/10J, DBA/2J, SJL/J, SWR/J, 129P3/J) and one outbred (CD-1) mouse strains. A minimum criterion sucrose intake (1 ml) under vehicle treatment, designed to avoid "floor effects" of antagonist treatment was not achieved in three (A/J, AKR/J, CBA/J) inbred mouse strains. Marked genetic variance in naltrexone's ability to inhibit sucrose intake was observed in the remaining strains with the greatest sensitivity observed in the C57BL/10J and C57BL/6J strains, intermediate sensitivity in BALB/cJ, C3H/HeJ, CD-1 and DBA/2J mice, and the least sensitivity in 129P3/J, SWR/J and SJL/J strains with a 7.5-36.5 fold range of greater effects in the ID(50) of naltrexone-induced inhibition in C57BL/10J relative to the three less-sensitive strains across the time course. Naltrexone primarily affected the maintenance, rather than the initiation of intake in BALB/cJ, CD-1, C3H/HeJ, DBA/2J and SJL/J mice, but significantly reduced sucrose intake at higher doses across the time course in C57BL/6J, C57BL/10J and 129P3/J mice. Whereas SWR/J mice failed to display any significant reduction in sucrose intake at any time point following any of the naltrexone doses, naltrexone's maximal magnitude of inhibitory effects was small (35-40%) in 129P3/J and SJL/J mice, moderate ( approximately 50%) in BALB/cJ, C3H/HeJ, CD-1 and DBA2/J mice, and profound (70-80%) in C57BL/6J and C57BL/10J mice. Indeed, the latter two strains displayed significantly greater percentages of naltrexone-induced inhibition of sucrose intake than virtually all other strains. These data indicate the importance of genetic variability in opioid modulation of sucrose intake.     

Genetically-associated variations in the development of reflex movements and synaptic junctions within an early reflex pathway of mouse spinal cord

The embryonic development of reflex forelimb movements produced by cutaneous stimulation of the forepaw was examined in five inbred strains of the house mouse, Mus musculus. A quantitative electron microscopic study of synapse formation between the neurons that comprise the spinal cutaneous reflex arc was also carried out on specimens from three of the strains subjected to reflex testing. This investigation provides evidence that there is significant genetically-associated variability in the developmental timing of synapse formation within this disynaptic pathway and in the reflex behavior which it mediates. Specifically, it was found that C57BL/6J embryos had greater numbers of synaptic junctions in the reflex pathway at embryonic days 14–16, and they also showed reflex movements earlier than LP/J embryos. C57BL/6J embryos also showed a more rapid increase in the number of boutons during this embryonic period. CBA/CaJ embryos displayed a temporal pattern of development that differed from both C57BL/6J and LP/J. At E15, CBA/CaJ embryos were more similar to LP/J with regard to both reflex activity and synapse number, but by E16, CBA/CaJ values for both of these measures were more similar to C57BL/6J. On the basis of the data detailed in the text, we suggest that the strains differ in the following manner: C57BL/6J embryos develop boutons rapidly but appear to be relatively inefficient in the actual formation of synaptic junctions; CBA/CaJ embryos develop boutons at a slower rate than C57BL/6J but form synaptic junctions more efficiently; LP/J embryos develop boutons slowly and are also relatively inefficient in forming synaptic junctions. The genetic implications of — and some developmental processes which might be responsible for — the observed strain differences in the timing of synaptic development are discussed in the text. There was no detectable genetic variability of the basic sequence in which the neurons of the cutaneous reflex arc develop their synaptic connections. For all three strains examined, the data indicated that synaptic closure occurred in a retrograde sequence with respect to the direction that neurotransmission normally flows between the neurons of this pathway. This finding agrees with results obtained by other investigators from a number of diverse vertebrate species, and such a widespread lack of variability implies that a retrograde sequencing of synapse formation is involved in the development of specific neuronal connectivities.     

Differential involvement of the dorsal hippocampus in passive avoidance in C57bl/6J and DBA/2J mice

The inferior performance of DBA/2 mice when compared to C57BL/6 mice in hippocampus-dependent behavioral tasks including contextual fear conditioning has been attributed to impaired hippocampal function. However, DBA/2J mice have been reported to perform similarly or even better than C57BL/6J mice in the passive avoidance (PA) task that most likely also depends on hippocampal function. The apparent discrepancy in PA versus fear conditioning performance in these two strains of mice was investigated using an automated PA system. The aim was to determine whether these two mouse strains utilize different strategies involving a different contribution of hippocampal mechanisms to encode PA. C57BL/6J mice exhibited significantly longer retention latencies than DBA/2J mice when tested 24 h after training irrespective of the circadian cycle. Dorsohippocampal NMDA receptor inhibition by local injection of the selective antagonist DL-2-amino-5-phosphonovaleric acid (AP5, 3.2 microg/mouse) before training resulted in impaired PA retention in C57BL/6J but not in DBA/2J mice. Furthermore, nonreinforced pre-exposure to the PA system before training caused a latent inhibition-like reduction of retention latencies in C57BL/6J, whereas it improved PA retention in DBA/2J mice. These pre-exposure experiments facilitated the discrimination of hippocampal involvement without local pharmacological intervention. The results indicate differences in PA learning between these two strains based on a different NMDA receptor involvement in the dorsal hippocampus in this emotional learning task. We hypothesize that mouse strains can differ in their PA learning performance based on their relative ability to form associations on the basis of unisensory versus multisensory contextual/spatial cues that involve hippocampal processing.     

Production of experimental allergic encephalomyelitis with the aid of pertussigen in mouse strains considered genetically resistant

Strains of mice (BALB/c An Bradley/Wehi, C57B1/10J, CBA/ca H Wehi, DBA/2 Wf, A/J Wehi), thought to be genetically resistant to experimental allergic encephalomyelitis (EAE) and known to be resistant to becoming hypersensitive to histamine after administration of pertussis vaccine were tested for their ability to develop EAE when purified pertussigen was included in the immunization. It was found that C57B1/10J, CBA/ca H Wehi, BALB/c An Bradley/Wehi and DBA/2 Wf developed typical signs and histologic evidence of EAE. The A/J Wehi and the B10D2/n Sn (not previously tested) strains developed only mild signs of EAE, while the known susceptible (SJL/J X BALB/c An Bradley/Wehi) F1 hybrids developed severe EAE. Histologic evidence of EAE was lacking in A/J Wehi mice and was minimal in B10D2/n Sn mice. These results suggest that neither the H-2 complex nor the gene controlling susceptibility to sensitization to histamine by administration of pertussigen are wholly responsible for susceptibility to EAE.     

Developmental expression of cell type-specific markers in mouse cerebellar cells in vitro

The expression of several cell type-specific markers was studied by indirect immunofluorescence in discontinuous BSA gradient fractionated and unfractionated mouse cerebellar cells cultured for 3 days in vitro from embryonic day 13 through postnatal day 9. Cell surface antigen NS-4 and tetanus toxin receptors are present at all ages studied. Thy-1 first detected on neurons with large cell bodies (Purkinje and/or Golgi Type II.neurons) onpostnatal day 3, but absent from all neurons with small cell bodies (granule, basket, and stellate cells). At all ages Thy-1 antigen is absent from astro- and oligodendroglia, and fibroblasts or fibroblast-like cells. Fibroblast-like cells express fibronectin at all ages studied. Astroglia expressing glial fibrillary acidic (GFA) protein are first detectable in cultures from 16-day-old embryos. Their number increases at later ages. At all ages studied fluorescein conjugated Ricinus communis agglutinin 120 brightly labels the cell surfaces of fibroblastic cells and large neurons, less brightly those of astrocytes, bu not those of small neurons. Oligodendroglia become detectable in cerebellar cultures from 16- and 17-day-old embryos maintained in vitro for 3 days using antibodies to 04 antigen and bovine corpus callosum, respectively. At embryonic ages BSA step gradient procedures do not result in enrichment of particular cell types as recognized by the available markers. From birth onward, however, enrichment of cell populations was obtained corresponding to the ones characterized at postnatal day 6 as described in the companion paper (Schnitzer and Schachner 1981b).     

Survey of embryonic stem cell line source strains in the water maze reveals superior reversal learning of 129S6/SvEvTac mice

The availability of pluripotent embryonic stem (ES) cells for gene targeting has resulted in laboratory mice becoming important animal models of human neurological disease. Inbred strains of mice differ in many behavioural phenotypes, such that the same gene mutation can appear to have different phenotypic effects when introduced onto different genetic backgrounds. Prior knowledge of the behavioural phenotypes of the inbred strains used for gene targeting would, therefore, allow the selection of the most appropriate genetic background for the hypothesis to be tested. With this in mind, we tested eight strains of mice (129S1/SvImJ, 129S2/SvPasIcoCrlBR, 129S6/SvEvTac, B6129SF1/J, C57BL/6J, C57BL/6N, LP/J and SM/J), including the sources of five ES cell lines commonly used for gene targeting, in the spatial (submerged platform) version of the Morris water maze, the most widely used paradigm to evaluate the cognitive abilities of genetically modified mice. The three 129 substrain sources of ES cell lines demonstrated spatial learning in the water maze that was superior to that of C57BL/6J, the inbred strain most commonly used for the maintenance and phenotypic testing of mutations. In addition, 129S6/SvEvTac was unique amongst the eight strains tested in having a particular capacity for reversal learning, when the submerged platform was relocated to the opposite quadrant. We conclude that some substrains of 129 could provide suitable genetic backgrounds for testing gene mutations that might be expected to impair cognitive function, thus negating the need to backcross to C57BL/6J, thereby avoiding the so-called "flanking gene problem".     

Water and Electrolyte Contents, Cell pH, and Membrane Potential of Primary Cultures of Astrocytes from DBA, C57, and SW Mice

Some basic properties of primary cultures of astrocytes derived from the cerebral cortex of an audiogenic seizure-sensitive strain of mice, DBA/2J (DBA), were studied with different approaches. The results were compared with those of audiogenic seizure-resistant strains, C57BL/6J (C57) and Swiss Webster (SW). Contents of intracellular water, protein, and DNA of DBA astrocytes were 0.673 +/- 0.019 ml/g cells, 0.082 +/- 0.006 g/g cells, and 0.0072 +/- 0.0005 g/g cells, respectively. These results are not different from those of either C57 or SW astrocytes. Intracellular concentration of K+, Na+, and Cl- ([K+]1, [Na+]1, and [Cl-]1) derived from the flame photometric and from the radioisotope uptake data of DBA astrocytes were 120.4 +/- 8.5, 25.9 +/- 3.2, and 26.8 +/- 1.8 mM/L cell H2O, respectively. [Na+]1 and [Cl-]1 in DBA astrocytes were lower than those in C57 and SW astrocytes. In DBA astrocytes, SITS decreased the cell/medium ratio (C/M) of 36Cl- and increased the C/M of 125I-; ouabain increased the C/M of 22Na+ and decreased the C/M of 125I-; bumetanide decreased the C/M of both 36Cl- and 22Na+; and NaClO4 decreased the C/M of 125I-. Similar results were observed in both C57 and SW astrocytes. Intracellular pH (pHi) as determined with 14C-DMO of astrocytes in HEPES-buffered saline solution averaged 7.04 +/- 0.03 for DBA, 7.01 +/- 0.02 for C57, and 6.97 +/- 0.02 for SW mice when pH of medium was maintained at 7.4. Modification of ion (HCO3-, Cl-, Na+, and K+) concentration and pH of culture medium all changed the pHi of astrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Induction of expression of the rat G5 nervous system antigen occurs postnatally

G5 is a cell membrane component found in high levels in the adult rat central nervous system and in low levels on some cells of the rat immune system. Binding assays with adult brain particulate protein preparations and monoclonal antibody to G5 (G5-IgG) gave highest activity in cerebral cortex and lowest in the white matter rich regions pons and spinal cord. Three peripheral nervous system components had no G5 activity. Analysis of G5 content in particulate protein preparations from whole rat brain of ages embryonic day 15 to adult indicates that G5 is present in negligible amounts in the newborn rat. It increases in both specific and total activity to reach adult levels by postnatal day 30. A similar induction curve was observed with cerebellum samples. In adult cerebellum, high levels of G5 were found in the molecular layer using both autoradiographic and immunofluorescence techniques. White matter had essentially no activity. The density and uniformity of reaction product in these techniques suggest that G5 is present on a major cellular constituent of the molecular layer. Pharmacologic experiments indicate G5 is not detectable on climbing fibers or adrenergic fibers. Cerebellar samples from juvenile rats also had predominant G5 activity in the forming molecular layer.     

MHC class II-positive perivascular microglial cells mediate resistance to Cryptococcus neoformans brain infection

Acquired resistance to the CNS pathogen Cryptococcus neoformans is mediated by CD4(+) T lymphocytes primed by exposure to antigen in the context of major histocompatibility class II (MHC II) molecules. In mouse brain, parenchymal and perivascular microglial cells may express interferon-gamma (IFN-gamma)-inducible MHC class II marker and thus interact with CD4(+) T cells. Primed effector T cells are retained in the infected CNS if antigen is encountered in proper MHC context and may deliver signals that potentiate microglia to enhanced fungistasis. Vaccinated C57BL6/J mice resist an ordinarily lethal C. neoformans rechallenge, but identically treated congenic Abeta(o/o) mice (MHC class II-deficient; CD4(+) T-cell-deficient) do not. Nor can Abeta(o/o) mice be adoptively immunized by infusion of lymphocytes from vaccinated C57BL6/J donors, as are severe combined immunodeficient (SCID) mice (MHC class II-intact, lymphocyte-deficient). Chimeric (C57BL/6J:Abeta(o/o)) mice with class II expression likely on perivascular microglia only were, like SCID mice, capable of adoptive immunization against C. neoformans brain infection. To the contrary, chimeric mice with class II expression likely only on parenchymal microglia were not capable of effective adoptive immunization against C. neoformans brain infection. Therefore, in order to mediate resistance to infection, primed CD4(+) T cells must interact with the replenishable perivascular microglial subset that lies in close proximity to cerebral vasculature. Although T cells may supply help in the form of inflammatory cytokines to parenchymal microglia, expression of class II on these cells appears unnecessary for antifungal activity.     

The influence of ImuVert, a biological response modifier, on the growth and ganglioside composition of murine neural tumors

ImuVert is a biological response modifier (BRM) that has antitumor effects in humans and rats. The influence of ImuVert on the ganglioside composition of two experimental brain tumors, ependymoblastoma and CT-2A, was studied in C57BL/6J mice. Gangliosides are expressed on plasma membranes and can serve as markers to distinguish neural cells from nonneural cells in mouse brain tumors.N- acetylneuraminic (NeuAc) is the predominant sialic acid in mouse neural cells, whereasN-glycolylneuraminic (NeuGc) is a major sialic acid in nonneural cells, e.g., macrophages and lymphocytes. ImuVert treatment increased the NeuGc ganglioside concentration in the ependymoblastoma, but had no effect on the sialic acid concentration in the CT-2A brain tumor. ImuVert also had a slight inhibitory effect on the growth of both brain tumors.     

Increased water temperature renders single-housed C57BL/6J mice susceptible to antidepressant treatment in the forced swim test

To investigate genotype x environment interactions in the forced swim test, we tested the influence of water temperature (20 degrees C, 25 degrees C, 30 degrees C) on floating behaviour in single-housed male C57BL/6J and BALB/c mice. We observed a contrasting relationship between floating and water temperature between the two strains, with C57BL/6J floating more and BALB/c floating less with increasing water temperature, independent of the lightening conditions and the time point of testing during the animals' circadian rhythm. Both strains showed an inverse relationship between plasma corticosterone concentration and water temperature, indicating that the differences in stress coping are unrelated to different perception of the aversive encounter. Treatment with desipramine (20mg/kg, i.p.) caused a reduction in immobility time in C57BL/6J mice if the animals were tested at 30 degrees C water temperature, with no effect at 25 degrees C and no effects on forced swim stress-induced corticosterone secretion. The same treatment failed to affect floating behaviour in BALB/c at any temperature, but caused a decrease in plasma corticosterone levels. Taken together we demonstrate that an increase in water temperature in the forced swim test exerts opposite effects on floating behaviour in C57BL/6J and BALB/c and renders single-housed C57BL/6J mice, but not BALB/c mice, susceptible to antidepressant-like behavioral effects of desipramine.     

A mouse model system for genetic analysis of sociability: C57BL/6J versus BALB/cJ inbred mouse strains.

BACKGROUND: Impairments in social behaviors are highly disabling symptoms of autism, schizophrenia, and other psychiatric disorders. Mouse model systems are useful for identifying the many genes and environmental factors likely to affect complex behaviors, such as sociability (the tendency to seek social interaction). To progress toward developing such a model system, we tested the hypothesis that C57BL/6J inbred mice show higher levels of sociability than BALB/cJ inbred mice. METHODS: Mice tested for sociability were 4- and 9-week-old, male and female C57BL/6J and BALB/cJ mice. On 2 consecutive days, the sociability of each test mouse toward an unfamiliar 4-week-old DBA/2J stimulus mouse was assessed with a social choice paradigm conducted in a three-chambered apparatus. Measures of sociability included the time that the test mouse spent near versus far from the stimulus mouse, the time spent directly sniffing the stimulus mouse, and the time spent in contact between test and stimulus mice in a free interaction. RESULTS: C57BL/6J mice showed higher levels of sociability than BALB/cJ mice overall in each of these measures. CONCLUSIONS: We propose that C57BL/6J and BALB/cJ mice will be a useful mouse model system for future genetic and neurobiological studies of sociability.     

Age dependence of strain determinant on mice motor coordination

Evaluation of motor coordination and motor learning in mice remains a challenge as many factors may interact with the different tests used. Among these factors, genetic background has been reported to be a major determinant of mice performances in motor coordination tests. However, it is not known if the strain dependence of motor coordination and motor learning remains constant through life. In order to assess this point, we tested during 5 days male and female mice of three different strains (NMRI, C57BL/6J, and C57BL/6J x 129OlaHsd) in runway, rotarod, and thin rod tests at juvenile (first day of testing = postnatal day 19) and adult (3 months) age. We found a strong strain effect on motor performances and motor learning at juvenile age (C57BL/6J performing more poorly than the two other strains), whatever the tests used. Interestingly, the C57BL/6J mice were the best performing mice at the adult age. These strain rankings were observed either in male and female groups. These results demonstrate that the strain determinant on mice performances and motor learning is highly age dependent.