Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice

Simpson, Elizabeth M.; Linder, C.; Sargent, Evelyn E.; Davisson, Muriel T.; Mobraaten, Larry E.; Sharp, John J.

doi:10.1038/ng0597-19

Cited by 650 publications

(459 citation statements)

References 27 publications

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“…Hence, the locomotor tests reported here were first validated with wildtype strains of various genetic backgrounds: B6, 129S5, 129P2 and F1 gen-erations (B6 × 129P2, B6 × 129S5). The latter two served as models for the CB−/− and PV−/− mice, respectively, since they were produced from either R1 or E14 embryonic stem cells, which are derived from either mice resembling 129S5 or from 129P2 mice, respectively [28]. In both cases, targeted ES cells had been injected into B6 blastocysts and the chimeras mated to B6 [11,12].…”

Section: Resultsmentioning

confidence: 99%

“…As the control groups for the mixed and B6 background, an F1 generation of B6 and 129P2 or B6PV+/+ littermates from heterozygous B6PV+/− breedings was used, respectively. Also for CB−/− mice produced from R1 stem cells [12], two different genetic backgrounds were tested: mice with a mixed background B6 and 129R1 (129Sv × 129SvJ) [28], or mice that had been backcrossed to B6 for seven generations (B6CB−/− and B6CB+/+, both derived from heterozygous B6CB+/− matings). Control mice for the B6 × 129R1 CB−/− background were either B6 × 129R1 CB+/+ littermates produced from heterozygous B6 × 129R1 CB+/− breedings or a F1 generation of B6 × 129S5, which was assumed to be similar to B6 × 129R1 [28].…”

Section: Subjectsmentioning

confidence: 99%

“…Also for CB−/− mice produced from R1 stem cells [12], two different genetic backgrounds were tested: mice with a mixed background B6 and 129R1 (129Sv × 129SvJ) [28], or mice that had been backcrossed to B6 for seven generations (B6CB−/− and B6CB+/+, both derived from heterozygous B6CB+/− matings). Control mice for the B6 × 129R1 CB−/− background were either B6 × 129R1 CB+/+ littermates produced from heterozygous B6 × 129R1 CB+/− breedings or a F1 generation of B6 × 129S5, which was assumed to be similar to B6 × 129R1 [28]. PV−/−CB−/− mice, which were bred from the mixed CB−/− and PV−/− mice [26] have a genetic background of B6 × 129P2 × 129R1 and were compared to a pool of 20 mice consisting of 10 each with a B6 × 129P2 or B6 × 129S5 background.…”

Section: Subjectsmentioning

confidence: 99%

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Differences in locomotor behavior revealed in mice deficient for the calcium-binding proteins parvalbumin, calbindin D-28k or both

FARRECASTANY

Schwaller

Gregory

et al. 2007

Behavioural Brain Research

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We investigated the role of the two calcium-binding proteins parvalbumin (PV) and calbindin D-28k (CB) in the locomotor activity and motor coordination using null-mutant mice for PV (PV−/−), CB (CB−/−) or both proteins (PV−/−CB−/−). These proteins are expressed in distinct, mainly non-overlapping populations of neurons of the central and peripheral nervous system and PV additionally in fast-twitch muscles. In a test measuring repeated locomotor activity during 18-20 days, the analysis revealed a slightly increased activity in mice lacking either protein, while the lack of both decreased the number of beams crossed during active periods. An increase in the characteristic speed during the first 8 days could be attributed to PVdeficiency, while the elimination of CB in CB−/− and double-KO mice decreased the percentage of fast movements at all time points. In the latter, additionally a reduction of the fastest speed was observed. The alterations in locomotor activity (fast movements, fastest speed) strongly correlate with the impairment in locomotor coordination in mice deficient for CB evidenced in the runway assay and the rotarod assay. The graded locomotor phenotype (CB > PV) is qualitatively correlated with alterations in Purkinje cell firing reported previously in these mice. The presence or absence of either protein did not affect the spontaneous locomotor activity when animals were placed in a novel environment and tested only once for 30 min. In summary, the lack of these calcium-binding proteins yields characteristic, yet distinct phenotypes with respect to locomotor activity and coordination.

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Section: Resultsmentioning

confidence: 99%

Section: Subjectsmentioning

confidence: 99%

Section: Subjectsmentioning

confidence: 99%

See 1 more Smart Citation

Differences in locomotor behavior revealed in mice deficient for the calcium-binding proteins parvalbumin, calbindin D-28k or both

FARRECASTANY

Schwaller

Gregory

et al. 2007

Behavioural Brain Research

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“…It is important to consider several caveats when interpreting the phenotypes of mutant mice; they include the potential for developmental compensations (Crawley 1996;Lathe 1996;Wilson and Tonegawa 1997), the influence of background genotype (Crawley 1996;Gerlai 1996;Sibilia and Wagner 1995;Simpson et al 1997;Threadgill et al 1995), and environmental factors such as diet and stress (Crabbe et al 1999). Such factors can result in unanticipated phenotypes, as exemplified by the NPY knockout mouse.…”

Section: Animal Models Of Obesitymentioning

confidence: 99%

Relevance of animal models to human eating disorders and obesity

2008

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Background and rationale This review addresses the role animal models play in contributing to our knowledge about the eating disorders anorexia nervosa (AN) and bulimia nervosa (BN) and obesity. Objectives Explore the usefulness of animal models in complex biobehavioral familial conditions, such as AN, BN, and obesity, that involve interactions among genetic, physiologic, psychological, and cultural factors. Results and conclusionsThe most promising animal model to mimic AN is the activity-based anorexia rodent model leading to pathological weight loss. The paradigm incorporates reward elements of the drive for activity in the presence of an appetite and allows the use of genetically modified animals. For BN, the sham-feeding preparation in rodents equipped with a gastric fistula appears to be best suited to reproduce the postprandial emesis and the defects in satiety. Animal models that incorporate genes linked to behavior and mood may clarify biobehavioral processes underlying AN and BN. By contrast, a relative abundance of animal models has contributed to our understanding of human obesity. Both environmental and genetic determinants of obesity have been modeled in rodents. Here, we consider single gene mutant obesity models, along with models of obesigenic environmental conditions. The contributions of animal models to obesity research are illustrated by their utility for identifying genes linked to human obesity, for elucidating the pathways that regulate body weight and for the identification of potential therapeutic targets. The utility of these models may be further improved by exploring the impact of experimental manipulations on the behavioral determinants of energy balance.

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“…These genetic manipulations, however, may complicate phenotypes resulting from developmental adaptations in the long-term presence of altered genes, requiring caution in interpreting results using these mice. Another potential confound of genetically modified mice is the fact that the backgrounds of the mice used for production show a wide span of genetic variation (e.g., Simpson et al, 1997), raising the question of whether the phenotypes of congenic mice in response to drugs result from the specific gene mutation or simply background traits. The most commonly used background strains in the production of knock-out, knock-in or transgenic animals are substrains of C57BL/6 and 129 mice.…”

Section: Introductionmentioning

confidence: 99%

C57BL/6J mice show greater amphetamine-induced locomotor activation and dopamine efflux in the striatum than 129S2/SvHsd mice

Chen

Zhang

Park

et al. 2007

Pharmacology Biochemistry and Behavior

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Inbred strains of mice have served as valuable models for studying genetic susceptibility to drug addiction, an alternative to genetically modified mouse models. This is the first study comparing amphetamine (AMPH) effects on locomotor stimulation and dopamine efflux between two inbred strains of mice C57BL/6J and 129S2/SvHsd, frequently used as background strains for production of genetically engineered mice. There were no significant differences in basal locomotor activity and basal dopamine levels between the two strains. However, C57BL/6J mice showed greater AMPHstimulated locomotor activity and AMPH-induced striatal dopamine efflux than 129S2/SvHsd mice. The differential AMPH effects could not be explained by differences in presynaptic dopamine components such as surface and total dopamine transporter (DAT) expression levels, striatal dopamine contents, and DAT activity. C57BL/6J and 129S2/SvHsd mice are excellent models for future identification of genetic, molecular, and behavioral components related to individual vulnerability to AMPH addiction. This study emphasizes the importance of mouse strain selections in the production of genetically modified mice for investigating phenotypes and mechanisms of psychostimulants.

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Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice

Cited by 650 publications

References 27 publications

Differences in locomotor behavior revealed in mice deficient for the calcium-binding proteins parvalbumin, calbindin D-28k or both

Differences in locomotor behavior revealed in mice deficient for the calcium-binding proteins parvalbumin, calbindin D-28k or both

Relevance of animal models to human eating disorders and obesity

C57BL/6J mice show greater amphetamine-induced locomotor activation and dopamine efflux in the striatum than 129S2/SvHsd mice

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