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PubMed2006

In vivo characterization of brain morphometric and metabolic endophenotypes in three inbred strains of mice using magnetic resonance techniques.

C57BL6J, FVB/N and 129/SvJ mice are commonly used as background strains to engineer genetic models of brain pathologies and psychiatric disorders. Magnetic resonance imaging (MRI) and spectroscopy provide alternative approaches to neuroanatomy, histology and neurohistochemistry for investigating the correlation between genes and brain neuroanatomy and neurometabolism in vivo. We used these techniques to non-invasively characterize the cerebral morphologic and metabolic endophenotypes of inbred mouse strains commonly used in neurological and behavioral research. We observed a great variability in the volume of ventricles and of structures involved in cognitive function (cerebellum and hippocampus) among these strains. In addition, distinct metabolic profiles were evidenced with variable levels of N-acetylaspartate, a neuronal marker, and of choline, a compound found in membranes and myelin. Besides, significant differences in high-energy phosphates and phospholipids were detected. Our findings demonstrate the great morphologic and metabolic heterogeneity among C57BL/ 6J, FVB/N and 129/SvJ mice. They emphasize the importance of selecting the appropriate genetic background for over-expressing or silencing a gene and provide some directions for modeling symptoms that characterize psychiatric disorders such as autism, schizophrenia and depression.

Animals↗
PubMed2004

The relative affective potency of glycine, L-serine and sucrose as assessed by a brief-access taste test in inbred strains of mice.

In general, rodents prefer both sucrose and L-serine relative to water and treat both compounds as possessing a similar taste quality (e.g. 'sweetness') despite that they are believed to bind with different T1R heterodimeric receptors in taste bud cells. We assessed the affective potency of these compounds along with glycine, which is thought to bind with both T1R receptor complexes, using a brief-access taste test in a gustometer. Unconditioned licking responses of two 'taster' strains (C57BL/6J and SWR/J), which display high preference for low concentrations of sucrose, and two 'non-taster' (129P3/J and DBA/2J) strains, which display blunted preference for low concentrations of sucrose, were measured during 5 s trials of varying concentrations of a single compound when mice (n=10/strain/stimulus) were non-deprived and when access to home-cage water was restricted. In non-deprived mice, sucrose generated monotonically increasing concentration-response curves regardless of strain, whereas glycine was only marginally effective at stimulating licking and L-serine produced relatively flat functions. The profile of responsiveness across strains was more complex than expected. For example, when tested with sucrose in the non-deprived condition, the 129P3/J non-taster strain surpassed the responsiveness of taster mice at mid-range to high concentrations. Under water-restricted conditions, these mice also were significantly more responsive to high concentrations of both sucrose and glycine compared with the other strains when stimulus licking was standardized relative to water. Thus, the affective potency of the stimuli tested here seems to be related to the ability of the compounds to bind with the T1R2+3 receptor complex. However, the profile of strain responsiveness to these tastants in the brief-access test does not appear to be simply explained by the sweetener 'taster' status of the strain.

Animals↗
PubMed1979

The role of macrophages in stimulation of immune induction and myelopoiesis: II: analysis of genetic restriction involved in the stimulation of granulocyte colony precursors or mature lymphocytes using factors prepared from different recombinant inbred strains of mice.

The genetic restriction involved in the reconstitution of immune responses in macrophage-depleted mouse spleen cultures, or the induction of colony formation in bone marrow cultures, by different molecular-weight species of lymphostimulatory molecules derived from mouse peritoneal cell suspensions is reported. The data suggest little evidence for genetic restriction in the ability of any of the factors to stimulate bone marrow colony formation in vitro. However, when immunological stimulation was investigated, a restriction coded for by genes in the K/D end of the MHC (70-90K factor) or in the I region of the MHC (30-45K factor) was observed. A third species of lymphostimulatory molecule (15K) showed no such restriction. Further evidence is presented to suggest that the active moiety in the 70-90K molecule(s) is a 15K-like species (nonrestricted in its ability to reconstitute cells from different strains of mice.

Animals↗
PubMed1993

Differences in expression of lupus nephritis in New Zealand mixed H-2z homozygous inbred strains of mice derived from New Zealand black and New Zealand white mice. Origins and initial characterization.

BACKGROUND: F1 hybrids of New Zealand Black (NZB) and New Zealand White (NZW) mice develop autoimmune glomerulonephritis resembling human lupus nephritis. Susceptibility to this complex autoimmune syndrome in humans and mice has been linked to genes mapping in or near the major histocompatibility complex that govern immune responses and levels of certain complement components. Previous studies showed that both parental strains contribute major histocompatibility complex-linked genes that are important for disease of the F1 hybrid. EXPERIMENTAL DESIGN: New inbred strains of New Zealand Mixed (NZM) mice were derived by selective inbreeding of progeny of a cross between NZB and NZW mice. Twelve of the 27 new NZM strains were selected for analysis. Mice were observed for up to 10 months of age to document the occurrence of nephritis and strain-specific differences in disease expression. H-2, Hc, and coat color loci were determined for each strain to establish homozygosity of NZB and NZW polymorphic markers. Strains were screened for the presence of anti-dsDNA autoantibodies. RESULTS: In some NZM strains early onset of lupus nephritis in females resembled the (NZB x NZW)F1 model, whereas in other strains early disease also occurred in males. Age at death and severity of nephritis vary among the lines; a few strains remain relatively free of glomerular lesions. Histocompatibility (H-2) typing showed that all strains are homozygous for the NZW haplotype (Ku, Au, Sz, Dz). Coat color analysis for four loci on chromosomes 2, 4, and 7 was consistent with specific reassortments and recombinations to explain the grey, tan, and white mice with red/pink eyes and the presence or absence of the fifth component of serum complement (C5) (Hc, chromosome 2). Anti-dsDNA autoantibodies were found in all but one of the NZM strains reported here. CONCLUSIONS: The NZM strains of mice are a unique set of inbred strains that have inherited various genomic segments of the two parental strains that lead to phenotypic differences in disease expression. These results indicate that the previously proposed strict requirement for H-2 heterozygosity for the development of nephritis in the (NZB x NZW)F1 hybrid mice may not be valid. It is assumed that both the Lpn-1 locus of NZB and the Lpn-2 locus of NZW and a sufficient number of other disease-associated genes of both ancestral strains have been recombined in these new strains to produce the various patterns of renal disease.

Animal Husbandry↗