Browsing by Subject "Mice, Inbred Strains"

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    The genetic susceptibility/resistance to fluorosis among different inbred mouse strains
    (2003) McHenry, Melissa A.K., 1971-; Everett, Eric T.; Dean, Jeffrey A.; Gonzalez-Cabezas, Carlos, 1966-; Jackson, Richard D.; Sanders, Brian J.; Stookey, George K.
    Fluoridation of community water supplies for the purpose of preventing dental caries remains one of the top 10 public health interventions of the last century. However, exposure (ingestion) of greater than optimal amounts of fluoride from a variety of sources has led to an increase in the prevalence of dental fluorosis. We propose that dental fluorosis represents a complex condition caused by environmental and genetic factors. Purpose: To assess the role of genetics in the pathogenesis of dental fluorosis using genetically separate inbred strains of mice. Methods: Twelve genealogically disparate strains of mice were treated with 0 ppm, 25 ppm, and 50 ppm of fluoride in their drinking water. Each mouse was given weekly dental fluorosis evaluations. After 60 days of treatment, femurs were collected for fluoride analysis. Mandibular incisors were isolated for quantitative light induced fluorescence (QLF) studies and fluoride analysis. Digital and 35 mm images were taken of all mouse incisors in order to apply and compare the Dean's Index and the modified Thylstrup and Fejerskov Index (TFI), both indices of dental fluorosis. Skeletal radiographs were taken on the euthanized mice and later examined for extra skeletal calcifications and other gross bony deformities. Results: Differences in dental fluorosis susceptibility/resistance were identified between the strains, ranging from mild, moderate, to severe dental fluorosis. Furthermore, we found clustering of strains into distinct phenotypic groups. The A/J mouse strain was highly susceptible, with a rapid onset and severe development of dental fluorosis compared with the other strains tested. The 129P3/J mouse strain was least affected with negligible dental fluorosis. From the skeletal radiographs, no gross skeletal lesions or evidence of bone dysplasia were noted. Similar body burden of fluoride, as judged from analysis of mineralized tissues, was seen in all strains despite differences in their predispositions to develop dental fluorosis. Both the Dean's and TF indices are useful for classifying the stage or severity of fluorosis in mice, and there are advantages to the use of digital images over conventional 35 mm slide images. Both indices correlate well with the amount of fluoride exposure during amelogenesis; however, these indices are not promising indicators of fluoride burden during amelogenesis. Conclusions: QLF proved to be an innovative and useful tool for the quantification of dental fluorosis. Furthermore, these observations support the role of a genetic component in the pathogenesis of fluorosis.
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    Genetics of Root Resorption Associated with Orthodontic Force in Mice
    (2006-07) Abass, Shaza K.; Hartsfield, James K., Jr.; Roberts, W. Eugene; Hock, Janet M.; Foroud, Tatiana M.; Everett, Eric T.
    External apical root resorption (EARR) is a common complication of orthodontic treatment. Genetic factors account for approximately 50% of the variation in EARR. Data have indicated variation in histological root resorption associated with orthodontic force (RRAOF) among different inbred strains of mice. Differences in expression of RANKL and OPG were investigated in two strains of mice with different susceptibility to RRAOF using irnmunohistochemistry. Increased localization of RANKL was detected in the tissues surrounding the root of the susceptible strain compared to the resistant strain and the controls. In contrast, increased localization of OPG was found in the tissues surrounding the roots in the resistant A/J strain compared to the susceptible DBA/2J strain. We conclude that differences in the expression of these key bone resorption mediators play a role in determining RRAOF susceptibility. Changes in serum TRAP 5b level in response to orthodontic force were investigated among female A/J, DBA/2J and BALB/cJ mice. The three strains differed in their TRAP positive cell numbers as well as their serum TRAP 5b level at baseline and when treated. A significant increase in the serum TRAP 5b level with treatment was only detected in the RRAOF susceptible DBA/2J strain, and not in RRAOF resistant strains. Our analysis indicates that differences in osteoclast/odontoclast activity play a role in susceptibility to RRAOF that is genetically determined. Serum TRAP 5b levels have a potential role in screening for individuals with greater susceptibility to root resorption. RRAOF was determined for male and female mice of the A/J, DBA/2J and BALB/cJ strains, as well as A/J x DBA/2J and A/J x BALB/cJ crosses. Sex differences were observed among the BALB/cJ strain only, with females more resistant to RRAOF when compared to males. Fis from the A/J x BALB/cJ cross were resistant suggesting that the A/J have dominant resistance alleles, while Fis from the A/J x DBA/2J cross had RRAOF intermediate between their parental A/J and DBA/2J mice, suggesting a polygenic trait. We concluded that the mode of inheritance of RRAOF in mice was polygenic in nature.
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    In vivo reference point indentation measurement variability in skeletally mature inbred mice
    (Nature Publishing Group, 2015) Srisuwananukorn, Andrew; Allen, Matthew R.; Brown, Drew M.; Wallace, Joseph M.; Organ, Jason M.; Department of Anatomy & Cell Biology, IU School of Medicine
    Reference point indentation (RPI) was developed to measure material-level mechanical properties of bone in vivo. Studies using RPI in vivo have discriminated between human subjects with previous skeletal fractures and those without and among dogs given different anti-remodeling drugs. Recently, this technology was extended to rats, providing the first in vivo data for rodents. The goal of the present study was to perform in vivo RPI measurements in mice, the most common animal model used to study bone. Twelve 16-week-old female C57BL/6 mice were subjected to RPI (three tests) on the anterior tibia, followed by a repeat test session on the contralateral limb 28 days later. A custom MATLAB program was used to derive several outcome parameters from RPI force-displacement curves: first cycle indentation distance (ID-1st), ID increase (IDI), total ID (TID), first cycle unloading slope (US-1st) and first cycle energy dissipation (ED-1st). Data within an individual were averaged across the three tests for each time point. Within-animal variation of all RPI parameters on day 1 ranged from 12.8 to 33.4% and from 14.1 to 22.4% on day 28. Between-animal variation on day 1 ranged from 11.4% to 22.8% and from 7.5% to 24.7% on day 28. At both time points, within- and between-animals, US-1st was the least variable parameter and IDI was most variable. All parameters were nonsignificantly lower at day 28 compared with day 1. These data are important to demonstrate the feasibility of collecting bone material property data longitudinally in mice and will inform the design of future studies in terms of statistical power and appropriate sample size considerations.
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    Normal mandibular morphology of inbred mouse strains
    (2004) Edwards, Michelle Halum; Everett, Eric T.; Hartsfield, James K., Jr.; Jamison, Paul L.; Ward, Richard E.; Dean, Jeffrey A.
    Even though the molecular events and pathways that underlie craniofacial development and morphogenesis are not fully understood, it is accepted that their orchestration is influenced by the interaction of genetic and environmental factors. Inbred mouse strains represent genetically homogenous groups of individuals. It is established that mice in one strain often differ quite remarkably from mice in other inbred strains. Those phenotypic differences make mice exceptional tools for the dissection of genetic factors that influence normal and abnormal craniofacial morphogenesis. While numerous investigations have focused on abnormal morphogenesis, a comprehensive study of normal craniometric morphology across multiple inbred strains of mice has not been previously performed. The Mouse Phenome Project, an international collaboration of investigators, was formed to systematically phenotype a collection of normal inbred mouse strains. The objectives of our studies were to determine and measure differences in quantitative mandibular traits/variables within and between different inbred mouse strains, and to assess sexual di1norphism through bilateral measuren1ents of the hemimandibles. These studies were a component of the Mouse Phenome Project to collect normal craniometric data from 12 genetically heterogeneous inbred strains utilizing digital images from equal numbers of female and male mice at 7 to 8 weeks of age. Our central hypothesis was that morphometric analysis of mandibular structures from genetically disparate inbred mouse strains would reveal quantifiable differences. The null hypothesis of no difference among the strains for 1nandibular measurements was rejected. Overall, CAST/Ei and MOLF/Ei were consistently small in size measured by body weight with small skeletal structures. There was no strong pattern of body weight and site of skeletal size in the mid and heavy weighted strains. Evidence of sexual dimorphism was supported. Overall, it appears males and females that have the least significance between them are in the DBA/2J strain, followed by A/J. The strain with the most significant difference between males and females is in the C3H/HeJ strain.
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    Normal Mandibular Morphology of Inbred Mouse Strains
    (2004) Edwards, Michelle Halum; Everett, Eric T.; Dean, Jeffrey A.; Hartsfield, James K.; Jamison, Paul L.; Ward, Richard E.
    Even though the molecular events and pathways that underlie craniofacial development and morphogenesis are not fully understood, it is accepted that their orchestration is influenced by the interaction of genetic and environmental factors. Inbred mouse strains represent genetically homogenous groups of individuals. It is established that mice in one strain often differ quite remarkably from mice in other inbred strains. Those phenotypic differences make mice exceptional tools for the dissection of genetic factors that influence normal and abnormal craniofacial morphogenesis. While numerous investigations have focused on abnormal morphogenesis, a comprehensive study of normal craniometric morphology across multiple inbred strains of mice has not been previously performed. The Mouse Phenome Project, an international collaboration of investigators, was formed to systematically phenotype a collection of normal inbred mouse strains. The objectives of our studies were to determine and measure differences in quantitative mandibular traits/variables within and between different inbred mouse strains, and to assess sexual dimorphism through bilateral measurements of the hemimandibles. These studies were a component of the Mouse Phenome Project to collect normal craniometric data from 12 genetically heterogeneous inbred strains utilizing digital images from equal numbers of female and male mice at 7 to 8 weeks of age. Our central hypothesis was that morphometric analysis of mandibular structures from genetically disparate inbred mouse strains would reveal quantifiable differences. The null hypothesis of no difference among the strains for mandibular measurements was rejected. Overall, CAST/Ei and MOLF/Ei were consistently small in size measured by body weight with small skeletal structures. There was no strong pattern of body weight and site of skeletal size in the mid and heavy weighted strains. Evidence of sexual dimorphism was supported. Overall, it appears males and females that have the least significance between them are in the DBA/2J strain, followed by A/J. The strain with the most significant difference between males and females is in the C3H/HeJ strain.
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    Relative fluid novelty differentially alters the time course of limited-access ethanol and water intake in selectively bred high-alcohol-preferring mice
    (Wiley Blackwell (Blackwell Publishing), 2015-04) Linsenbardt, David N.; Boehm, Stephen L.; Department of Psychology, School of Science
    BACKGROUND: The influence of previous alcohol (ethanol [EtOH])-drinking experience on increasing the rate and amount of future EtOH consumption might be a genetically regulated phenomenon critical to the development and maintenance of repeated excessive EtOH abuse. We have recently found evidence supporting this view, wherein inbred C57BL/6J (B6) mice develop progressive increases in the rate of binge EtOH consumption over repeated drinking-in-the-dark (DID) EtOH access sessions (i.e., "front loading"). The primary goal of this study was to evaluate identical parameters in high-alcohol-preferring (HAP) mice to determine whether similar temporal alterations in limited-access EtOH drinking develop in a population selected for high EtOH preference/intake under continuous (24-hour) access conditions. METHODS: Using specialized volumetric drinking devices, HAP mice received 14 daily 2-hour DID EtOH or water access sessions. A subset of these mice was then given 1 day access to the opposite assigned fluid on day 15. Home cage locomotor activity was recorded concomitantly on each day of these studies. The possibility of behavioral/metabolic tolerance was evaluated on day 16 using experimenter-administered EtOH. RESULTS: The amount of EtOH consumed within the first 15 minutes of access increased markedly over days. However, in contrast to previous observations in B6 mice, EtOH front loading was also observed on day 15 in mice that only had previous DID experience with water. Furthermore, a decrease in the amount of water consumed within the first 15 minutes of access compared to animals given repeated water access was observed on day 15 in mice with 14 previous days of EtOH access. CONCLUSIONS: These data further illustrate the complexity and importance of the temporal aspects of limited-access EtOH consumption and suggest that previous procedural/fluid experience in HAP mice selectively alters the time course of EtOH and water consumption.