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Differences in liver ganglioside patterns in various inbred strains of mice.

The ganglioside patterns in the liver of different inbred and hybrid strains of mice were investigated. The inbred strains were Balb/cAnNCr1BR, C57BL/6NCr1BR, DBA/2NCr1BR. C3H/HeNCr1BR; the hybrid strain was the Swiss albino. The following major gangliosides were found to be present in mouse liver: GM3-NeuAc; GM3-NeuGl, GM2 [a mixture of one species carrying N-acetylneuraminic acid (NeuAc) and one carrying N-glycollylneuraminic acid (NeuGl)], GM1 and GD1a-(NeuAc,NeuGl). The qualitative and quantitative patterns of liver gangliosides were markedly different in the various inbred strains of mice; in Balb/cAnNCr1BR strain, ganglioside GM2 was preponderant (99.2% of total ganglioside content); in C57BL/6NCr1BR, the major ganglioside was GM2 (90.4%), followed by GM3-NeuAc (5.6%) and GM3-NeuGl (4.0%); in DBA/2NCr1BR, GM2 accounted for 77.1%, GD1a-(NeuAc,NeuGl) 18.9% and GM1 3.1% of gangliosides; in C3H/HeNCr1BR, GM2 constituted 50.6%, GM1 22.8% and GD1a-(NeuAc,NeuGl) 22.1%. In the hybrid Swiss albino mice, liver ganglioside composition markedly varied from one animal to another, GM3-NeuGl, GM2 and GD1a-(NeuAc,NeuGl) being the predominant gangliosides in the various cases.

Animals↗

Identification of inbred strains of mice and genetic relationships between strains as assessed by DNA fingerprinting.

Strain identification and the assessment of genetic relationships among inbred strains of mice were examined by DNA fingerprinting using M13 phage DNA as a probe. We used 8 inbred strains (NC/Jah, DDD/Jah, DSD/Jah, RR/Jah, SS/Jah, C3H/HeJah, C57BL/6 Jah and C57BL/6CrSlc) and coisogenic (NC-brp) as well as congenic (C57BL/6-bg) strains. DNA fingerprints using M13 phage DNA as a probe revealed identical patterns within strains. Bands due to new mutations in minisatellite regions within each strain were not observed. The banding patterns were strain-specific. Thus, DNA fingerprinting seemed to be suitable for genetic monitoring of mice. A dendrogram constructed with difference values calculated from DNA fingerprint patterns showed that relationships among strains reflected the history of these strains, so DNA fingerprinting could also be effectively used to assess the relationships between inbred strains of mice.

Animals↗

Genetic differences in phenytoin pharmacokinetics. In vivo clearance and in vitro metabolism among inbred strains of mice.

Plasma phenytoin elimination rates were examined among twelve inbred strains of mice. Two populations are identified--the 'fast metabolizers' (BALB/cN, C57BL/6N, C57BL/6J, AKR/N, AKR/J and C3H/HeN) having almost exactly twice as rapid an elimination rate as the 'slow metabolizers' (CL/FR, CBA/J, DBA/2N, STAR/N, SJL/N, DBA/2J and RF/N). The difference in elimination rate between C57BL/6J and DBA/2J cannot be accounted for by dissimilarities in volume of distribution. The phenytoin elimination rate in the (C57BL/6J)(DBA/2J)F1 heterozygote is expressed as an additive trait. A good correlation exists between phenytoin elimination rates in vivo and phenytoin metabolism by liver microsomes in vitro, as determined by a newly described assay using high-performance liquid chromatography. 3-Methylcholanthrene pretreatment does not enhance phenytoin elimination or metabolism. The cytochrome P-450-mediated monoxygenase metabolism of phenytoin is not associated with the Ah locus or with coat color among progeny of the (C57BL/6N)(DBA/2N) F1 x DBA/2N backcross. Phenobarbital pretreatment enhances phenytoin elimination and metabolism in both a fast metabolizer (C57BL/6N) and a slow metabolizer (DBA/2N) strain. Phenobarbital pretreatment probably also induces non-P-450 enzymes, such as those which form the phenytoin dihydrodiol and the glucuronide and glutathione conjugates, in addition to inducing one or more forms of P-450 that oxygenate phenytoin. These data probably reflect allelic differences in a structural gene encoding for one (or more) form(s) of control cytochrome P-450 that metabolizes phenytoin, rather than allelic differences in a regulatory gene. The marked sensitivity of inbred mouse strains CL/FR and A/J and the marked resistance of STAR/N, Swiss-Webster, and C57BL/6 to phenytoin-induced cleft lip and/or palate cannot be explained by genetic differences in phenytoin elimination rates or liver microsomal metabolism in vitro, as measured by the methods described in this report.

Animals↗

[Changes in cholinergic mechanisms and in learning in three strains of inbred mice after electric stimulation of the dorsal hippocampus].

Two experiments investigated the neurochemical correlates of hippocampal stimulation effects on learning in three inbred strains of Mice. In the 1st experiment, it was shown that subseizure electrical stimulation of the dorsal hippocampus, 30 sec. after a partial appetitive learning session (1) improved 24 hrs. delayed performances of BALB/c Mice (2) had little but significant effect on C57BL/6 (3) had no effect on C57BR animals. The second experiment was aimed at studying the stimulation effect on hippocampal cholinergic mechanisms by testing the two main enzymes involved in acetylcholine synthesis and degradation (choline acetyltransferase = ChAc and acetylcholinesterase = AChE). The major findings of this experiment were as follows: (1) stimulation induced a 3 hrs. delayed improvement of ChAc activity for the BALB/c strain (2) a similar but less important effect was observed in C57BL/6 Mice (3) there was no effect for C57BR animals. These result further support the view that cholinergic hippocampal mechanisms act upon memory consolidation.

Acetylcholinesterase↗

In vitro brain acetylcholinesterase response among three inbred strains of mice to monocrotophos.

The strain differences in the neurotoxic potential of monocrotophos (MCP) were assessed by determining the inhibition of brain acetylcholinesterase (AChE) in BALB/cAnN, DBA/2J and C57BL/6J in vitro. MCP being a competitive inhibitor for AChE, alters the Km values widely among these inbred strains. Comparatively least alterations in Km were found in BALB/cAnN and maximum in DBA/2J. Based on the Ki values DBA/2J was found to be the most sensitive strain to MCP inhibition followed by C57BL/6J and BALB/cAnN.

Acetylcholinesterase↗

A QTL for the genetic variance in free-running period and level of locomotor activity between inbred strains of mice.

Many genes support the manifestation of the circadian period in mice. In a multiple-gene trait all genes contributing in a minor way to this characteristic are quantitative trait loci (QTL). Screens of both the BXD and the CXB panels of recombinant inbred mice suggested that distal chromosome 1, between 90 and 100 cM, contained a QTL, Cplaq3, for a difference in the circadian period of locomotor activity between the C57BL/6J and the DBA/2J and between the BALB/cBy and the C57BL/6By progenitor strains. The mice studied were a commercially available congenic strain, B6.D2-Mtv7a/Ty, from 50 to 100 days old. This congenic strain contains a small DBA/2J genomic insert that covers the region of the provisional QTL in a 99.9% C57BL/6J background. The congenic mice had a shorter period than C57BL/6J mice, confirming that this region has a QTL for the difference in period between the C57BL/6J and the DBA/2J strains. In addition, these data suggest that this region has a QTL for the mean amount of daily activity and for the pattern of locomotor activity.

Alleles↗

Comparative study of American cutaneous leishmaniasis and diffuse cutaneous leishmaniasis in two strains of inbred mice.

Two Leishmania strains, AZV (isolated from a typical case of American cutaneous leishmaniasis) and AMP (from a case of diffuse cutaneous leishmaniasis), were studied in C57BL/6 and BALB/c mice. After infection with 10(4) amastigotes of either strain, C57BL/6 mice developed self-resolving lesions lasting 20 to 23 weeks and showed both delayed hypersensitivity response to leishmanial antigen and specific agglutinating antibodies. On the other hand, BALB/c mice infected with 10(4) AZV or AMP amastigotes developed chronic, large, ulcerated lesions and showed impaired cellular and humoral responses to the parasite. When BALB/c and C57BL/6 mice received 10(2) AMP amastigotes, patterns of infection were similar to those observed after inoculation of 10(4) amastigotes. In vitro studies revealed that spleen cells from AZV- or AMP-infected C57BL/6 mice showed an increased DNA-synthetic response to leishmanial antigen, concanavalin A, and phytohemagglutinin. Spleen cells from AZV- or AMP-infected BALB/c mice showed an increased response to concanavalin A and diminished responses to leishmanial antigen, phytohemagglutinin, and lipopolysaccharide.

Animals↗

A comparative study of craniofacial growth during secondary palate development in four strains of mice.

Different inbred strains of mice have different timing of palatal shelf elevation, and strains with normally late shelf elevation have been shown to be more susceptible to induction of cleft palate. However, the major factors controlling the timing of elevation remain unknown. The objective of this study was to analyze different strains of mice morphometrically in order to identify characteristics or changes that corresponded with and contributed to shelf elevation. The four strains--A/J, SWV, C3H, and C57BL/6J (C57)--were studied between days 13 and 16 of gestation. Similar patterns of facial development were present in the strains, with C57 fetuses most advanced and A/J fetuses least advanced, relative to chronological age. Lifting of the head away from the thorax was also most retarded in the A/J fetuses. Palatal shelf elevation occurred between 200 and 240 mg body weight, with C57 fetuses smaller than A/J fetuses. The time of shelf elevation corresponded with the time that Meckel's cartilage became longer than the oronasal cavity, and the time that the head position lifted rapidly. Simultaneously with elevation, the height of the oral cavity increased and the width of the oral cavity decreased. The decrease in maxillary width appeared to facilitate shelf contact during palatal closure. The results demonstrated the need for normal growth of Meckel's cartilage for shelf elevation when a normal tongue was present between the palatal shelves. The results also showed that facial growth is one of the important factors that determine the time of palatal shelf elevation in mice.

Animals↗