Telemetric recording of sleep and home cage activity in mice

STUDY OBJECTIVES: This study assessed differences in spontaneous sleep and locomotor activity in inbred and hybrid mouse strains and evaluated telemetry for recording sleep in mice. DESIGN: Uninterrupted recordings of sleep and home cage activity were obtained in four mouse strains. Pre-operative and post-operative home cage activity was obtained in two strains. SETTINGS: N/A PARTICIPANTS: The subjects were mice of three inbred (C57BL/6J (B6), n=25; BALB/cJ (C), n=24; DBA/2J (D2), n=30) strains and one hybrid (CB6F1/J (CB6: C x B6), n=19) strain. INTERVENTIONS: Electroencephalogram (EEG) and activity were recorded by telemetry, and behavioral states were visually scored based on EEG and activity records. Home cage activity was determined utilizing photobeam interruptions. MEASUREMENTS AND RESULTS: 1) Among the three inbred strains: C mice had the least sleep and the greatest amount of activity; D2 mice exhibited the least non-rapid-eye-movement (NREM) sleep, the longest average NREM-bout length, and the greatest diurnal ratio of sleep and were the most inactive; B6 mice had the most sleep and an intermediate activity level; no differences among inbred strains were observed in total REM. The CB6 mice exhibited intermediate levels of total sleep and activity and had greater amounts of REM compared to its parental strains. 2) Total operative mortality was 9.3%, with all deaths occurring within 3 to 9 days after the operation; significant reductions in activity were observed after the operation. CONCLUSION: Differences in spontaneous sleep and activity exist among inbred and hybrid mouse strains. Accurate determination of sleep states in mice can be achieved with telemetrically recorded EEG and activity.     

The resistance of BALB/cJ mice to Yersinia pestis maps to the major histocompatibility complex of chromosome 17

Yersinia pestis, the causative agent of plague, has been well studied at the molecular and genetic levels, but little is known about the role that host genes play in combating this highly lethal pathogen. We challenged several inbred strains of mice with Y. pestis and found that BALB/cJ mice are highly resistant compared to susceptible strains such as C57BL/6J. This resistance was observed only in BALB/cJ mice and not in other BALB/c substrains. Compared to C57BL/6J mice, the BALB/cJ strain exhibited reduced bacterial burden in the spleen and liver early after infection as well as lower levels of serum interleukin-6. These differences were evident 24 h postinfection and became more pronounced with time. Although a significant influx of neutrophils in the spleen and liver was exhibited in both strains, occlusive fibrinous thrombi resulting in necrosis of the surrounding tissue was observed only in C57BL/6J mice. In an effort to identify the gene(s) responsible for resistance, we measured total splenic bacteria in 95 F(2) mice 48 h postinfection and performed quantitative trait locus mapping using 58 microsatellite markers spaced throughout the genome. This analysis revealed a single nonrecessive plague resistance locus, designated prl1 (plague resistance locus 1), which coincides with the major histocompatibility complex of chromosome 17. A second screen of 95 backcrossed mice verified that this locus confers resistance to Y. pestis early in infection. Finally, eighth generation backcrossed mice harboring prl1 were found to maintain resistance in the susceptible C57BL/6J background. These results identify a novel genetic locus in BALB/cJ mice that confers resistance to Y. pestis.     

The association between lung innate immunity and differential airway antigen- specific immune responses

The mechanisms involved in the differential regulation of airwayimmune responses in atopic versus non-atopic individuals arepoorly understood. In this study, the association between nonspecific immunity and the differential airway antigen-specificImmune responses was examined in a murine model. The disparityIn antigen-specific IgE and IgG2a productions between the twostrains of mice was observed to be significant. C57BL/6J micewere much more efficient than BALB/cJ mice in making IgE antibodyto Inhaled ovalbumin (OVA) antigen. On the contrary, BALB/cJmice did make more IgG2a antibodies than C57BL/6J mice to InhaledOVA. These findings suggest that in C57BL/6J mouse strain apredominant T_h 2 type of Immune response develops in responseto inhaled OVA antigen. In contrast, BALB/c mice mount a T_h1 type of immune response to aerosollzed OVA antigen. Furthermore,after lipopolysaccharlde (LPS) stimulation, the IL-12 mRNA expressionof lung-derived cells from BALB/cJ mice was higher than thatfrom C57BL/6J cells. However, the lung-derived cells of C57BL/6Jmice stimulated by LPS produced higher levels of IL-b and prostaglandinE than BALB/cJ lung-derived cells did. Therefore, our studydemonstrated that the difference of lung-derived cells in theirability to produce cytokine and prostaglandln between BALBIcJand C57BL/6J mice correlates well with the type of the airwayantigen-specific immune effector functions.     

Maternal influences on adult stress and anxiety-like behavior in C57BL/6J and BALB/cJ mice: a cross-fostering study

The quality of maternal care during early life has a dramatic impact on later stress reactivity and anxiety. Two inbred mouse strains, C57BL/6J and BALB/cJ, differ in levels of maternal care, stress reactivity, and anxiety-like behavior in adulthood. However, the relative contribution of early environmental factors and genetic predisposition to differences in these strains is not known. Maternal care, plasma corticosterone levels, emotionality, and hippocampal and paraventricular nucleus (PVN) glucocorticoid receptor mRNA levels were measured in adult C57BL/6J and BALB/cJ mice. Litters were then cross-fostered and anxiety-like behavior and stress reactivity was assessed in adulthood. Significantly less maternal care and elevated stress-induced corticosterone and emotionality was observed in BALB/cJ compared to C57BL/6J mice. Yet, no strain differences were found in hippocampal or paraventricular nucleus glucocorticoid receptor mRNA levels. Cross-fostering did alter anxiety-like behavior and basal corticosterone levels, which suggests that while genetic differences account for some of the variations between these two strains early rearing conditions also contribute.     

Mouse strain differences in operant self-administration of ethanol

By the use of operant conditioning procedures, we determined whether mice from two strains, C57BL/6J and BALB/cJ, differ in ethanol-reinforced behavior. To establish ethanol as a reinforcer, drinking was induced by feeding mice prior to the 30-min experimental session. Initially mice received water and then a series of increasing ethanol concentrations (1, 2, 4, and 8%, w/v) in response to a lever press. The volume of liquid consumed per unit of body weight remained relatively constant across concentrations, and thus the amount of ethanol consumed (g/kg) increased with increases in ethanol concentration. At all concentrations the C57BL/6J mice drank larger volumes than the BALB/cJ mice. After shifting the time of feeding from before to after the session, the consumption of 8% ethanol declined 56% for the C57B/6J mice and 81% for the BALB/cJ mice. To determine if ethanol was serving as a reinforcer, behavior and intake were then compared during ethanol and water availability. The ethanol consumption of the C57BL/6J mice markedly exceeded the water consumption and resulted in blood ethanol levels of 199 ±27 mg/dl. These levels significantly exceeded the 8% ethanol intake of the BALB/cJ mice, while 0% intake was low and not significantly different between strains. The 8% ethanol drinking of the BALB/cJ mice did not differ from their water drinking. Thus, ethanol was established as a positive reinforcer for C57BL/6J mice but not for BALB/cJ mice.This research was supported in part by New Investigator Research Awards AA-06104 and AA-06924 to Frank R. George from the National Institute on Alcohol Abuse and Alcoholism and by Research Scientist Development Award DA-00007 to Richard A. Meisch from the National Institute on Drug Abuse.     

Strain differences in sleep patterns of healthy and influenza-infected inbred mice

Influenza-infected C57BL/6J and BALB/cByJ mice respectively develop increased slow-wave sleep (SWS) during the dark phase and reduced SWS during the light phase of the 24 hour circadian cycle. To determine whether similar or alternative variations in SWS develop after influenza infection in other inbred strains of mice, we characterized the sleep patterns of additional strains both before and after influenza infection. Three strains (A/J, BALB/cByJ, and C3H/HeJ) showed light-phase SWS suppression, two strains (C57BL/6J and DBA/2J) showed dark-phase SWS enhancement, and one strain (A/J) showed dark-phase SWS suppression. Three strains (AKR/J, C57BR/cdJ, and FVB/NJ) did not show significant changes in SWS time on day two post-inoculation. Core temperatures were correlated to change in SWS time after infection, but were not correlated to SWS during the baseline period. These data support and expand the existing literature that indicates genetic modulation of sleep both in healthy mice and in mice undergoing viral infection.     

Ozone-induced acute pulmonary injury in inbred mouse strains

To determine if host factors influence the time course and extent of lung injury after acute inhalation of ozone (O3), we evaluated the physiologic and biologic response of nine genetically diverse inbred strains of mice (C57BL/6J, 129/SvIm, BTBR, BALB/cJ, DBA/2J, A/J, FVB/NJ, CAST/Ei, and C3H/HeJ) exposed to O3 (2.0 ppm x 3 h). Whole lung lavage determined that 129/Svlm, BTBR, DBA/2J, and FVB/NJ had a peak increase in polymorphonuclear cells (PMNs) at 6 h, whereas C57BL/6J and CAST/Ei had a peak increase at 24 h after exposure; airway PMNs were minimally elevated in A/J and C3H/HeJ; BALB/cJ had a predominant lymphocytic influx. Interleukin-6 concentration in the lavage fluid was associated with the influx of PMNs, whereas the total protein in the lavage fluid did not always correlate with lavage cellularity. Respiratory responses were monitored using whole body plethysmography and enhanced pause index. C57BL/6J, BALB/cJ, 129/SvIm, and BTBR were highly sensitive to O3 and exhibited significant increases in enhanced pause to methacholine aerosol stimulation at 6 and 24 h after exposure to O3. In contrast, DBA/2J, A/J, FVB/NJ, CAST/Ei, and C3H/HeJ strains had demonstrated increases in sensitivity to MCh at 6 h after exposure, but responses had returned to near baseline by 24 h after exposure to O3. Epithelial cell proliferation as assessed by proliferating cell nuclear antigen staining was evident at 24 h after exposure to O3. C57BL/6J and A/J showed 4% proliferating cell nuclear antigen-positive cells; 129/SvIm, DBA/2J, and FVB/NJ had 1-3%; and BTBR, BALB/cJ, CAST/Ei, and C3H/HeJ had < 1%. Phenotypic measurements in six inbred strains were used for an in silico genome analysis based on the Roche mouse database. Consistent loci on chromosomes 1, 7, and 15 were among those identified to have a significant association with the phenotypes studied. In aggregate, our approach has identified O3-resistant (C3H/HeJ and A/J) and -vulnerable (C57BL/6J and 129/SvIm) strains of mice, and determined novel genomic loci, suggesting a clear genetic basis for the lung response to inhaled O3.     

Widespread natural variation in murine natural killer T-cell number and function

Natural killer T (NKT) cells comprise a novel T-lymphocyte subset that can influence a wide variety of immune responses through their ability to secrete large amounts of a variety of cytokines. Although variation in NKT-cell number and function has been extensively studied in autoimmune disease-prone mice, in which it has been linked to disease susceptibility, relatively little is known of the natural variation of NKT-cell number and function among normal inbred mouse strains. Here, we demonstrate strain-dependent variation in the susceptibility of C57BL/6J and BALB/cJ mice to NKT-mediated airway hyperreactivity, which correlated with significant increases in serum interleukin-4 (IL-4) and IL-13 elicited by the synthetic glycosphingolipid alpha-galactosylceramide. Examination of NKT-cell function revealed a significantly greater frequency of cytokine-producing NKT cells in C57BL/6J versus BALB/cJ mice as well as significant differences in the kinetics of NKT-cell cytokine production. Extension of this analysis to a panel of inbred mouse strains indicated that variability in NKT-cell cytokine production was widespread. Similarly, an examination of NKT-cell frequency revealed a significantly greater number of liver NKT cells in the C57BL/6J mice versus BALB/cJ mouse livers. Again, examination of a panel of inbred mouse strains revealed that liver NKT-cell numbers were quite variable, spanning over a 100-fold range. Taken together, these results demonstrate the presence of widespread natural variation in NKT-cell number and function among common inbred mouse strains, which may have implications for the examination of the influence of NKT cells in immune responses and disease pathogenesis among different genetic backgrounds.     

Maternal influences on adult stress and anxiety‐like behavior in C57BL/6J and BALB/CJ mice: A cross‐fostering study

The quality of maternal care during early life has a dramatic impact on later stress reactivity and anxiety. Two inbred mouse strains, C57BL/6J and BALB/cJ, differ in levels of maternal care, stress reactivity, and anxiety‐like behavior in adulthood. However, the relative contribution of early environmental factors and genetic predisposition to differences in these strains is not known. Maternal care, plasma corticosterone levels, emotionality, and hippocampal and paraventricular nucleus (PVN) glucocorticoid receptor mRNA levels were measured in adult C57BL/6J and BALB/cJ mice. Litters were then cross‐fostered and anxiety‐like behavior and stress reactivity was assessed in adulthood. Significantly less maternal care and elevated stress‐induced corticosterone and emotionality was observed in BALB/cJ compared to C57BL/6J mice. Yet, no strain differences were found in hippocampal or paraventricular nucleus glucocorticoid receptor mRNA levels. Cross‐fostering did alter anxiety‐like behavior and basal corticosterone levels, which suggests that while genetic differences account for some of the variations between these two strains early rearing conditions also contribute. © 2005 Wiley Periodicals, Inc. Dev Psychobiol 48: 95–96, 2006.     

Influence of contextual fear on sleep in mice: a strain comparison

STUDY OBJECTIVES: This study assessed the influence of contextual fear on sleep in inbred and hybrid mouse strains. DESIGN: Uninterrupted baseline recordings of sleep were obtained for 3 days in 3 mouse strains. After baseline sleep recording sessions, fear-conditioned mice were presented 15 shock presentations on 4 consecutive days. Control mice were subjected to the same procedures except that they never received shock. Sleep was examined after shock training and after exposure to the shock context alone. SETTINGS: N/A. PARTICIPANTS: The subjects were mice of 2 inbred (C57BL/6J [B6], N=15; BALB/cJ [C], N=19) strains and 1 hybrid (CB6F1/J [CB6: C x B6], N=17) strain. INTERVENTIONS: Electroencephalograms (EEG) and activity were recorded by telemetry, and behavioral states were visually scored based on EEG and motor activity records. MEASUREMENTS AND RESULTS: Shock training selectively reduced rapid eye movement (REM) sleep in mice compared to time-matched baseline recordings. The reduction of REM sleep was significantly greater in the reactive C and the F1 hybrid strain compared to the less reactive B6 strain. Posttraining exposure to the context alone reduced REM sleep in much the same manner as exposure to the footshock, with the CB6 hybrid mice exhibiting greater alterations in sleep and a greater reduction of REM sleep. In contrast, mice that did not receive shock training showed increased REM sleep after being returned to the chamber. CONCLUSION: Aversive events and the fearful contexts that become associated with them can alter sleep in much the same way. Sleep disruptions after an aversive event or its reminders vary with genetic background.     

Evidence of Thymus-Independent Local and Systemic Antibody Responses to Cryptosporidium parvum Infection in Nude Mice

Differences in susceptibility to persistent cryptosporidial infection between two strains of adult athymic nude mice prompted us to investigate the immune mechanism(s) that may control resistance to infection in these T-cell-deficient mice. We studied fecal oocyst shedding, serum and fecal parasite-specific antibody responses, and fecal immunoglobulin levels in athymic C57BL/6J nude and athymic BALB/cJ nude mice following oral inoculation with Cryptosporidium parvum oocysts at 8 to 9 weeks of age. C57BL/6J nude mice had significantly higher fecal parasite-specific immunoglobulin A (IgA) (days 27, 31, 35, and 42 postinoculation) and IgM (days 10, 17, 24, 28, 31, 38, 42, and 48 postinoculation) levels than BALB/cJ nude mice (P < 0.05) and significantly higher serum parasite-specific IgA levels at 63 days postinoculation (P < 0.03). Moreover, C57BL/6J nude mice shed significantly fewer C. parvum oocysts than BALB/cJ nude mice from days 52 to 63 postinoculation (P < 0.05). In contrast, BALB/cJ nude mice had higher levels of non-parasite-specific IgA (days 38 to 63 postinoculation) and IgM (days 24, 35, 38, and 52 postinoculation) than C57BL/6J nude mice in feces (P < 0.05). These data suggest that parasite-specific fecal antibodies may be associated with resistance to C. parvum in C57BL/6J nude mice.     

Influence of shock training and explicit fear-conditioned cues on sleep architecture in mice: strain comparison

Fear conditioning is thought to model anticipatory anxiety. Inbred mouse strains exhibit different levels of reactivity to aversive environmental stimuli, which may reflect anxiety. We examined the effects of fear conditioning on sleep in mouse strains that differ on behavioral measures of anxiety. Mice (BALB/cJ [C], C57BL/6J [B6], CB6F1/J [CB6], n = 7–10 per strain) were implanted with transmitters for recording sleep by telemetry. Baseline sleep was recorded, and the mice were trained to associate a cue (tone) with footshock (15 cue–shock pairings on 4 consecutive days). Sleep was recorded after shock training and again 4 to 5 days later after presentation of the cue alone. Shock training produced a relatively selective suppression of rapid eye movement sleep (REM) that was greater in the C strain compared to the B6 and CB6 mice. Post-training exposure to the cue alone suppressed REM in all strains. The C strain exhibited a relatively greater immediate suppression of REM, and the CB6 hybrid mice showed the greatest overall suppression of REM. These data demonstrate that stimuli associated with an aversive event can alter sleep and suppress REM in much the same way as exposure to the event itself. Fear conditioning may provide a model for examining genetic and neural mechanisms underlying the influence of anxiety on sleep.     

Genetic analysis of cerebellar foliation patterns in mice (Mus musculus)

Four inbred strains of mice, DBA/2J, C57BL/10J, BALB/cJ, and SJL/J, were mated in a diallel cross. The cerebella of the F₁ generation were examined for the presence (Type I) or absence (Type II) of an intraculminate fissure between vermian lobule IV and vermian lobule V (the ventral and dorsal lobules of the culmen). One strain (DBA/2J) consistently expressed the Type I pattern. Another strain (SJL/J) expressed predominantly the Type II pattern. The other two strains (C57BL/10J and BALB/cJ) and many of the hybrids exhibited variability in their expression of the foliation patterns. The results were analyzed using biometrical genetic procedures and showed significant additive and dominance genetic effects and a maternal effect. Correlations of these cerebellar anatomical variants with the development of behavior are discussed.     

Differential effects of lorazepam on sleep and activity in C57BL/6J and BALB/cJ strain mice

Compared to C57BL/6 mice, BALB/c mice exhibit greater 'anxiousness' on behavioural tests of anxiety, and can show significantly longer sleep disruptions after exposure to anxiogenic situations. Relative to C57BL/6 mice, BALB/c mice also have reduced benzodiazepine (BZ) receptor densities in the brain and fivefold less BZ receptor density in the amygdala, a region important in anxiety and in the control of arousal. Lorazepam is a BZ receptor full agonist and has been used to treat both anxiety and insomnia. Differences between C57BL/6 and BALB/c mice raise the question of whether BZ agonists would impact sleep and activity differentially in the two strains. We examined the effects of two doses of lorazepam (0.5 and 1.5 mg kg⁻¹) or saline alone (0.2 mL) on sleep and activity in C57BL/6 ( n  =   8) and BALB/c ( n  =   7) mice. Compared to saline, both doses of lorazepam significantly increased non-rapid eye movement (NREM) and reduced activity in both strains. In C57BL/6 mice, rapid eye movement (REM) was increased at both doses. In BALB/c mice, the 0.5 mg kg⁻¹ dose had no significant influence on REM, whereas REM was reduced significantly after the 1.5 mg kg⁻¹ dose. The results demonstrate significant differences between C57BL/6 and BALB/c mice in the effects of lorazepam on REM, whereas the effects on NREM and activity were similar. Strain differences in the number of BZ receptors in the amygdala, but not other brain regions, suggests possible site specificity in the effects of lorazepam on REM. These differences in BZ-binding sites in the amygdala could be a significant factor in differences in the sleep response between C57 and BALB/c mice.     

Accelerated re-entrainment to advanced light cycles in BALB/cJ mice

Circadian rhythms in mammals are coordinated by the suprachiasmatic nuclei (SCN) of the hypothalamus, which are most potently synchronized to environmental light–dark cycles. Large advances in the light–dark cycle typically yield gradual advances in activity rhythms on the order of 1–2 h per day until re-entrainment is complete due to limitations on the circadian system which are not yet understood. In humans, this delay until re-entrainment is accomplished is experienced as jetlag, with accompanying symptoms of malaise, decreased cognitive performance, sleep problems and gastrointestinal distress. In these experiments, locomotor rhythms of BALB/cJ mice monitored by running wheels were shown to re-entrain to large 6- or 8-hour shifts of the light–dark cycle within 1–2 days, as opposed to the 5–7 days required for C57BL/6J mice. A single-day 6-hour advance of the LD cycle followed by release to constant darkness yielded similar phase shifts, demonstrating that exaggerated re-entrainment is not explained by masking of activity by the light–dark cycle. Responses in BALB/cJ mice were similar when monitored instead by motion detectors, indicating that wheel-running exercise does not influence the magnitude of responses. Neither brief (15 min) light exposure late during subjective nighttime nor 6-hour delays of the light–dark cycle produced exaggerated locomotor phase shifts, indicating that BALB/cJ mice do not merely experience enhanced sensitivity to light. Fos protein was expressed in cells of the SCN following acute light exposure at ZT10 of their previous light–dark cycle, a normally non-responsive time in the circadian cycle, but only in BALB/cJ (and not C57BL/6J) mice that had been subjected two days earlier to a single-day 6-hour advance of the light–dark cycle, indicating that their SCN had been advanced by that treatment. BALB/cJ mice may thus serve as a useful comparative model for studying molecular and physiological processes that limit responsiveness of circadian clocks to photic input.     

Genetic variance contributes to ingestive processes: a survey of 2-deoxy-D-glucose-induced feeding in eleven inbred mouse strains

The feeding response following administration of the anti-metabolic glucose analogue, 2-deoxy-d-glucose (2DG), is conceptualized as an experimental model of glucoprivation, which may contribute to the understanding of inter-individual differences in glucose and carbohydrate intake and, ultimately, obesity. Although variation in the intake of several nutrients as well as food and water are known to be associated with genetic variation, it is not known whether 2DG-induced feeding is similarly genotype dependent. The present study therefore examined 2DG-induced feeding in mice of 11 inbred (A/J, AKR/J, BALB/cJ, CBA/J, C3H/HeJ, C57BL6/J, C57BL10/J, DBA/2J, SJL/J, SWR/J, 129P3/J) and one outbred (CD-1) strains across a wide range of previously determined effective 2-DG doses (200, 400, 600, 800 mg/kg) and test times (1-4 h). Orderly dose-dependent increases in 2DG-induced feeding occurred after all four doses in outbred CD-1 and inbred DBA/2J mice, across the three highest doses for BALB/cJ, SJL/J and 129P3/J mice, and across the two highest doses for CBA/J and AKR/J mice. Limited instances of 2DG-induced feeding were noted only at the highest dose in A/J and C3H/HeJ mice, or at a moderate dose in C57BL/6J mice. Further, the full 2DG dose range failed to alter food intake in C57BL/10J mice, and produced significant reductions in food intake in SWR/J mice. Food intake after 2DG doses of 200-600 mg/kg, but not 800 mg/kg, displayed significant cross-correlation, suggesting that large 2DG doses may recruit non-specific effects upon food intake. There was no correlation between food intake in the absence (vehicle baseline) of and presence of 2DG, suggesting that the regulation of glucose intake in non-challenged mice does not predict subsequent responses to glucoprivic challenge. The data demonstrate genotype-dependent variability in this glucoprivic response, and may provide the basis for the subsequent identification of trait-relevant genes.     

Physiological function and behavioral genetics. I. Genetic variance for peripheral conduction velocity in mice

Individual differences for conduction velocity in the ventral and dorsal caudal nerves of 856 mice were assessed employing a rapid,in vivo procedure. Analysis of conduction velocity differences for mice of six inbred strains (A/J, BALB/cJ, CBA/J, C3H/HeJ, C57BL/6J, and DBA/1J) suggests that individual differences for conduction velocity are influenced by genetic differences. Animals of the BALB/cJ and CBA/J strains displayed significantly higher speeds of conduction than those of the C3H/HeJ and A/J strains. Conduction velocities for DBA/1J and C57BL/6J animals did not differ significantly from those of the other strains. Results of three studies allowing assessment of effects of strain, female and male parent, sex, and interactions among these factors support the findings of the strain comparison with regard to genetic variance for peripheral nerve conduction velocity. In addition, these studies indicate heterosis for fast speed of conduction. More detailed genetic analyses are in progress.This research was supported by NSF grant GU 2591 and NIH grant NS 09536.     

Differential immune response in two handled inbred strains of mice

C57BL/10J and BALB/cJ mice, outfostered at birth to C3H/2Ibg dams were subjected to handling on days 1 through 20 of life. Their plaque forming cell (PFC) response to sheep red blood cells as adults on day 5 post-immunization was compared to the PFC response in non-handled control mice. The PFC response of handled C57BL/10J mice was significantly suppressed compared to the PFC response in non-handled mice while the response of the handled and non-handled BALB/cJ mice was not significantly different.     

Genetic control of susceptibility to Porphyromonas gingivalis-induced alveolar bone loss in mice

Periodontal disease affects a large percentage of the human population. Resorption of the alveolar bone of the jaw is a pivotal sequela of periodontal disease, because this bone is the attachment site for the periodontal ligaments that anchor the teeth. Using a murine model in which alveolar bone loss is induced by oral infection with Porphyromonas gingivalis, a gram-negative bacterium associated with human adult periodontal disease, we provide evidence suggesting that susceptibility to such bone loss is a genetically determined trait. AKR/J, DBA/2J, and BALB/cByJ or BALB/cJ mice were highly susceptible, while A/J, A/HeJ, 129/J, SJL/J, and C57BL/6J mice were much more resistant. When susceptible BALB/cJ and BALB/cByJ mice were crossed to resistant strains, two patterns were observed. (BALBc/ByJ x C57BL/6J)F(1) offspring were susceptible, suggesting C57BL/6J has recessive resistance alleles, while (BALB/cJ x A/J)F(1) mice were all resistant, suggesting that A/J mice have dominant resistance alleles. These results suggest a tractable genetic basis for P. gingivalis-induced alveolar bone loss and open the possibility of exploiting the mouse model to identify loci important for host susceptibility and resistance to periodontal disease.