C57BL/6J Background (c57bl/6j + background)

Distribution by Scientific Domains


Selected Abstracts


Multiple Genetic Loci From CAST/EiJ Chromosome 1 Affect vBMD Either Positively or Negatively in a C57BL/6J Background,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2006
Bouchra Edderkaoui
Abstract Skeletal phenotype analyses of 10 B6.CAST-1 congenic sublines of mice have revealed evidence for the presence of three closely linked QTLs in Chr 1 that influence femoral vBMD both positively and negatively. Introduction: BMD is an important component of bone strength and a recognized predictor of risk for osteoporotic fracture. Our goal in this study was to fine map the chromosomal location of volumetric BMD (vBMD) quantitative trait loci (QTLs) in mouse distal chromosome 1 (Chr 1). Materials and Methods: After several backcrosses of the B6.CAST-1T congenic strain, which carried the initial BMD QTL in Chr 1 with B6 mice, the N10F1 generation mice were intercrossed to obtain recombinations that yielded different regions of the QTL. Thirty-eight polymorphic markers were used to fine map the initial 1T QTL region (100-192 Mb). Different skeletal parameters were compared between the 10 sublines and B6 female mice at 16 weeks of age. A t -test was used to determine the significant difference between sublines and B6 control mice, whereas one-way ANOVA and posthoc (Newman-Keuls) tests were performed to compare the phenotype between the sublines. Results: Significantly higher femur vBMD was found in sublines that carried cast alleles from 100 to 169 and 172 to 185 Mb of the centromere compared with the B6 control mice (10-12%, p < 0.001). However, sublines that carried cast alleles from 185 to 192 Mb showed significantly lower femur vBMD compared with the control mice (,6%, p < 0.05). Furthermore, femur vBMD phenotype showed a negative correlation with endosteal circumference (r = ,0.8, p = 0.003), and a strong correlation with cortical thickness for combined data from the 10 sublines (r = 0.97, p < 0.001). Moreover, a high correlation was found between body weight and both periosteal and endosteal circumferences for sublines carrying cast alleles from 167 to 175, 168 to 185, and 169 to 185 Mb, whereas no significant correlation was found between these parameters for sublines carrying cast alleles from 172 to 185 Mb. Conclusions: Genetic analysis using congenic sublines revealed that the initial BMD QTL on Chr 1 is a complex site with multiple loci affecting bone phenotypes, showing the value of the congenic approach in clearly identifying loci that control specific traits. [source]


Hypolocomotion, anxiety and serotonin syndrome-like behavior contribute to the complex phenotype of serotonin transporter knockout mice

GENES, BRAIN AND BEHAVIOR, Issue 4 2007
A. V. Kalueff
Although mice with a targeted disruption of the serotonin transporter (SERT) have been studied extensively using various tests, their complex behavioral phenotype is not yet fully understood. Here we assess in detail the behavior of adult female SERT wild type (+/+), heterozygous (+/,) and knockout (,/,) mice on an isogenic C57BL/6J background subjected to a battery of behavioral paradigms. Overall, there were no differences in the ability to find food or a novel object, nest-building, self-grooming and its sequencing, and horizontal rod balancing, indicating unimpaired sensory functions, motor co-ordination and behavioral sequencing. In contrast, there were striking reductions in exploration and activity in novelty-based tests (novel object, sticky label and open field tests), accompanied by pronounced thigmotaxis, suggesting that combined hypolocomotion and anxiety (rather than purely anxiety) influence the SERT ,/, behavioral phenotype. Social interaction behaviors were also markedly reduced. In addition, SERT ,/, mice tended to move close to the ground, frequently displayed spontaneous Straub tail, tics, tremor and backward gait , a phenotype generally consistent with ,serotonin syndrome'-like behavior. In line with replicated evidence of much enhanced serotonin availability in SERT ,/, mice, this serotonin syndrome-like state may represent a third factor contributing to their behavioral profile. An understanding of the emerging complexity of SERT ,/, mouse behavior is crucial for a detailed dissection of their phenotype and for developing further neurobehavioral models using these mice. [source]


Stem cell factor rescues tyrosinase expression and pigmentation in discreet anatomic locations in albino mice

PIGMENT CELL & MELANOMA RESEARCH, Issue 6 2009
Jillian C Vanover
Summary The K14-SCF transgenic murine model of variant pigmentation is based on epidermal expression of stem cell factor (SCF) on the C57BL/6J background. In this system, constitutive expression of SCF by epidermal keratinocytes results in retention of melanocytes in the interfollicular basal layer and pigmentation of the epidermis itself. Here, we extend this animal model by developing a compound mutant transgenic amelanotic animal defective at both the melanocortin 1 receptor (Mc1r) and tyrosinase (Tyr) loci. In the presence of K14-Scf, tyrosinase-mutant animals (previously thought incapable of synthesizing melanin) exhibited progressive robust epidermal pigmentation with age in the ears and tails. Furthermore, K14-SCF Tyrc2j/c2j animals demonstrated tyrosinase expression and enzymatic activity, suggesting that the c2j Tyr defect can be rescued in part by SCF in the ears and tail. Lastly, UV sensitivity of K14-Scf congenic animals depended mainly on the amount of eumelanin present in the skin. These findings suggest that c-kit signaling can overcome the c2j Tyr mutation in the ears and tails of aging animals and that UV resistance depends on accumulation of epidermal eumelanin. [source]


Hypothalamic-Pituitary-Adrenal Axis Abnormalities in Response to Deletion of 11,-HSD1 is Strain-Dependent

JOURNAL OF NEUROENDOCRINOLOGY, Issue 11 2009
R. N. Carter
Inter-individual differences in hypothalamic-pituitary-adrenal (HPA) axis activity underlie differential vulnerability to neuropsychiatric and metabolic disorders, although the basis of this variation is poorly understood. 11,-Hydroxysteroid dehydrogenase type 1 (11,-HSD1) has previously been shown to influence HPA axis activity. 129/MF1 mice null for 11,-HSD1 (129/MF1 HSD1,/,) have greatly increased adrenal gland size and altered HPA activity, consistent with reduced glucocorticoid negative feedback. On this background, concentrations of plasma corticosterone and adrenocorticotrophic hormone (ACTH) were elevated in unstressed mice, and showed a delayed return to baseline after stress in HSD1-null mice with reduced sensitivity to exogenous glucocorticoid feedback compared to same-background genetic controls. In the present study, we report that the genetic background can dramatically alter this pattern. By contrast to HSD1,/, mice on a 129/MF1 background, HSD1,/, mice congenic on a C57Bl/6J background have normal basal plasma corticosterone and ACTH concentrations and exhibit normal return to baseline of plasma corticosterone and ACTH concentrations after stress. Furthermore, in contrast to 129/MF1 HSD1,/, mice, C57Bl/6J HSD1,/, mice have increased glucocorticoid receptor expression in areas of the brain involved in glucocorticoid negative feedback (hippocampus and paraventricular nucleus), suggesting this may be a compensatory response to normalise feedback control of the HPA axis. In support of this hypothesis, C57Bl/6J HSD1,/, mice show increased sensitivity to dexamethasone-mediated suppression of peak corticosterone. Thus, although 11,-HSD1 appears to contribute to regulation of the HPA axis, the genetic background is crucial in governing the response to (and hence the consequences of) its loss. Similar variations in plasticity may underpin inter-individual differences in vulnerability to disorders associated with HPA axis dysregulation. They also indicate that 11,-HSD1 inhibition does not inevitably activate the HPA axis. [source]