Previous studies have concluded that the development of polydipsia (PD, a daily water intake ≥ 21 ml) among captive Danish bank voles, is associated with the development of a type 1 diabetes (T1D), ...based on findings of hyperglycaemia, glucosuria, ketonuria/-emia, lipemia, destroyed beta cells, and presence of autoantibodies against GAD65, IA-2, and insulin.
We retrospectively analysed data from two separate colonies of Danish bank voles in order to 1) estimate survivorship after onset of PD, 2) evaluate whether the weight of PD voles differed from non-PD voles, and, 3), evaluate a state of PD as a practical and non-invasive tool to screen for voles with a high probability of hypeglycaemia. In addition, we discuss regional differences related to the development of diabetes in Scandinavian bank voles and the relevance of the Ljungan virus as proposed etiological agent.
We found that median survival after onset of PD is at least 91 days (lower/upper quartiles = 57/134 days) with a maximum recording of at least 404 days survivorship. The development of PD did not influence the weight of Danish bank voles. The measures of accuracy when using PD as predictor of hyperglycaemia, i.e. sensitivity, specificity, positive predictive value, and negative predictive value, equalled 69%, 97%, 89%, and 89%, respectively.
The relatively long survival of Danish PD bank voles suggests potentials for this model in future studies of the long-term complications of diabetes, of which some observations are mentioned. Data also indicates that diabetes in Danish bank is not associated with a higher body weight. Finally, the method of using measurements of daily water intake to screen for voles with a high probability of hyperglycaemia constitutes a considerable refinement when compared to the usual, invasive, methods.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of this study was to examine whether voles performing stereotypic behaviours (Ster) differed in physical welfare from voles, which did not develop stereotypies (N-Ster). The chosen variables ...were reproductive success and capacity to survive barren housing conditions. Furthermore, effect of weight on proneness to develop stereotypic behaviours were examined. Singly housed Ster (
n
=
62) in barren cages showed superior survival when compared to similar housed N-Ster (
n
=
38;
p
=
0.002). Furthermore, Ster females (
n
=
25) gave birth to both a first and second litter faster than N-Ster females (
n
=
14;
p
≤
0.019). Litter size, number of weanlings and proportion of barren females did not differ between Ster and N-Ster, but pups from Ster experienced a higher pre-weaning mortality in the second litter (
p
=
0.0095). Voles classed as Ster within age 6 month (
n
=
55) weighed less than same aged N-Ster (
n
=
45) already from weaning (21 days;
p
=
0.0204). However, weight at weaning, whether LIGHT (weight
≤
median;
n
=
47) or HEAVY (weight
>
median;
n
=
53), had no effect on subsequent development of stereotypies in terms of either onset age or fraction which developed stereotypies. The results suggested that Ster had better physical welfare, as reflected in better survival, than N-Ster when housed singly and a higher reproductive success when used as breeders.
Handling-induced seizures observed among 23 of 333 captive born bank voles was characterized by tonic/clonic convulsions, occasionally accompanied by an apparent loss of consciousness. Seizures were ...never observed among wild caught voles (
N
=
71). Median age for first observation of seizures was 157 days. Median latency to onset following mild handling was 12.6
s and median time to resumption of normal behaviour after arrest of convulsions was 28.05
s. Consecutive daily tests to provoke seizures indicated that more seizures were elicitated on the first day of testing (25.6%) compared to the following 4 test-days (8.7%). Incidence of seizure prone (SP) voles declined from 10.2% in F1 to 5.1% in F2 with no sex bias. A possible explanation for this decline could be that all F1 voles (
N
=
118) descended from non-stereotyping (N-Ster) parents where the majority of F2 voles (
n
=
138) descended from two stereotyping (Ster) parents: incidence of SP voles were five times higher among offspring from N-Ster parents than Ster parents (10–11% vs. 2.2%;
p
<
0.0001). However, the development of stereotypic behaviours did not affect seizure proneness. Roughly one-third of the captive born voles developed diabetes. However, the disease did not affect seizure proneness. SP voles were distributed among the litters (
n
=
60) in accordance with the negative binomial distribution, which indicate a “lumped” distribution. The proportion of SP voles which had SP full siblings, was significantly higher than the proportion of non-SP voles having SP full siblings (15/23 vs. 30/310,
p
=
0.0001), which, taken together, suggest the possibility for future establishment of lines differing in seizure proneness.
Previous studies have concluded that the development of polydipsia (PD, a daily water intake greater than or equal to21 ml) among captive Danish bank voles, is associated with the development of a ...type 1 diabetes (T1D), based on findings of hyperglycaemia, glucosuria, ketonuria/-emia, lipemia, destroyed beta cells, and presence of autoantibodies against GAD65, IA-2, and insulin. We retrospectively analysed data from two separate colonies of Danish bank voles in order to 1) estimate survivorship after onset of PD, 2) evaluate whether the weight of PD voles differed from non-PD voles, and, 3), evaluate a state of PD as a practical and non-invasive tool to screen for voles with a high probability of hypeglycaemia. In addition, we discuss regional differences related to the development of diabetes in Scandinavian bank voles and the relevance of the Ljungan virus as proposed etiological agent. We found that median survival after onset of PD is at least 91 days (lower/upper quartiles = 57/134 days) with a maximum recording of at least 404 days survivorship. The development of PD did not influence the weight of Danish bank voles. The measures of accuracy when using PD as predictor of hyperglycaemia, i.e. sensitivity, specificity, positive predictive value, and negative predictive value, equalled 69%, 97%, 89%, and 89%, respectively. The relatively long survival of Danish PD bank voles suggests potentials for this model in future studies of the long-term complications of diabetes, of which some observations are mentioned. Data also indicates that diabetes in Danish bank is not associated with a higher body weight. Finally, the method of using measurements of daily water intake to screen for voles with a high probability of hyperglycaemia constitutes a considerable refinement when compared to the usual, invasive, methods.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Wild bank voles (Clethrionomys glareolus) may develop diabetes in laboratory captivity. The aim of this study was to test whether bank voles develop type 1 diabetes in association with Ljungan virus. ...Two groups of bank voles were analyzed for diabetes, pancreas histology, autoantibodies to glutamic acid decarboxylase (GAD65), IA-2, and insulin by standardized radioligand-binding assays as well as antibodies to in vitro transcribed and translated Ljungan virus antigens. Group A represented 101 trapped bank voles, which were screened for diabetes when euthanized within 24 hours of capture. Group B represented 67 bank voles, which were trapped and kept in the laboratory for 1 month before being euthanized. Group A bank voles did not have diabetes. Bank voles in group B (22/67; 33%) developed diabetes due to specific lysis of pancreatic islet beta cells. Compared to nondiabetic group B bank voles, diabetic animals had increased levels of GAD65 (P < .0001), IA-2 (P < .0001), and insulin (P = .03) autoantibodies. Affected islets stained positive for Ljungan virus, a novel picorna virus isolated from bank voles. Ljungan virus inoculation of nondiabetic wild bank voles induced beta-cell lysis. Compared to group A bank voles, Ljungan virus antibodies were increased in both nondiabetic (P < .0001) and diabetic (P = .0015) group B bank voles. Levels of Ljungan virus antibodies were also increased in young age at onset of newly diagnosed type 1 diabetes in children (P < .01). These findings support the hypothesis that the development of type 1 diabetes in captured wild bank voles is associated with Ljungan virus. It is speculated that bank voles may have a possible zoonotic role as a reservoir and vector for virus that may contribute to the incidence of type 1 diabetes in humans.
Wild bank voles (Clethrionomys glareolus) kept in the laboratory under barren housing conditions develop high incidences of type 1 diabetes mellitus due to beta cell-specific lysis in association ...with the appearance of GAD65, IA-2, and insulin autoantibodies. Wild-caught and immediately analyzed voles show no histological signs of diabetes, and the disease may therefore be induced by circumstances related to the housing of the animals in captivity. We tested the possibility that postnatal stress by either maternal separation or water immersion at different intervals would induce diabetes in adult bank voles. We found that low-frequent stress during the first 21 days of life increases, whereas high-frequent stress markedly reduces, the incidence of type 1 diabetes in adulthood. These results differentiate the role of early-experienced stress on subsequent type 1 diabetes development and emphasize that the bank vole may serve as a useful new animal model for the disease.
Wild bank voles ( Clethrionomys glareolus ) may develop diabetes in laboratory captivity. The aim of this study was to test whether bank voles develop type 1 diabetes in association with Ljungan ...virus. Two groups of bank voles were analyzed for diabetes, pancreas histology, autoantibodies to glutamic acid decarboxylase (GAD65), IA‐2, and insulin by standardized radioligand‐binding assays as well as antibodies to in vitro transcribed and translated Ljungan virus antigens. Group A represented 101 trapped bank voles, which were screened for diabetes when euthanized within 24 hours of capture. Group B represented 67 bank voles, which were trapped and kept in the laboratory for 1 month before being euthanized. Group A bank voles did not have diabetes. Bank voles in group B (22/67; 33%) developed diabetes due to specific lysis of pancreatic islet beta cells. Compared to nondiabetic group B bank voles, diabetic animals had increased levels of GAD65 ( P < .0001), IA‐2 ( P < .0001), and insulin ( P = .03) autoantibodies. Affected islets stained positive for Ljungan virus, a novel picorna virus isolated from bank voles. Ljungan virus inoculation of nondiabetic wild bank voles induced beta‐cell lysis. Compared to group A bank voles, Ljungan virus antibodies were increased in both nondiabetic ( P < .0001) and diabetic ( P = .0015) group B bank voles. Levels of Ljungan virus antibodies were also increased in young age at onset of newly diagnosed type 1 diabetes in children ( P < .01). These findings support the hypothesis that the development of type 1 diabetes in captured wild bank voles is associated with Ljungan virus. It is speculated that bank voles may have a possible zoonotic role as a reservoir and vector for virus that may contribute to the incidence of type 1 diabetes in humans.
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