Paresis of peristalsis and ileus lead to death in lactating mice

32
Laboratory
Animals
(1986) 20, 32-35.
Paresis of peristalsis and ileus lead to death in lactating mice*
I. KUNSTYR
/nstitllt fiir Versuchstierkllnde im Zentralen Tierlabor, Medizinische Hochschu/e Hannover,
D-3000 Hannover 6/, Federal Republic of Germany
Summary
Based on the examination of'45 dead and 5 moribund
female mice during a 2-year period, we are able to
describe a new disease entity: ileus of the small
intestine in lactating mice caused by a paresis of'
peristalsis. Diarrhoea was not observed and
innammation and infectious agents were not found.
Females were affected during the 2nd week of their
first lactation.
The condition
may have a mortality
rate as high as 40%. It is assumed that exhaustion
(calcium, glucose, etc.) is the cause of this condition.
Consequentl}', the development of' a dietary supplement or of'a special diet for lactating mice may prove
beneficial in preventing this disease. Endogenic
(Clostridia) or exogenic toxic components may also
playa role.
Keywords: Mice; Gastrointestinal system, gastrointestinal motility; Lactation.
During
post-mortem
examinations
of breeding
female mice which died spontaneously
during lactation, we noticed unusual changes in the digestive
tract not described for any known infectious agent.
Between
October
1982 and October
1984, we
examined a total of 50 mice with this syndrome and
our results have led us to discover a new disease
which we refer to as paresis (partial paralysis) of
peristalsis and ileus in lactating mice.
Material and methods
50 affected lactating mice were examined.
All of
them were kept in the Institute as either breeding
females or as experimental
animals for mutagenicity
testing (Fahrig, 1981). Housing and feeding conditions have been previously
described
(Kunstyf,
Matthiesen,
Giirtner,
Maess & Heimann,
1982).
The mice were fed a standardized
pelleted diet for
breeding mice and rats (Altromin
1310 from Altromin Spezialfutterwerke
GmbH,
0-4937 Lage,
FRG).
Examination
included
necropsy,
photodocumentation
and bacteriological
observations.
"Partly
Malm(i
Received
presented
during the 2nd FELASA
18-20 June. 1984.
25
lalll/ary
NBS.
Accepted
symposiulll,
25 AI/gust
/985.
Bacteriological
techniques
comprised
routine
cultivation
of aerobes
and anaerobes
(Kunstyf,
1983) and at a later phase (in about 15 animals)
anaerobic cultures were instigated and direct smears
(Gram stain) of the intestinal contents were examined to rule out Clostridia. In four cases special
techniques
for Campy/ohacler sp. were
used
(Weber, Lembke & Schafer, (982). The animal
strain was recorded, as well as the day of lactation,
litter size, and the number and age of the young.
The organs of 3 mice were examin~d histologically.
Results
Of 50 affected females, 45 were presented dead for
necropsy and 5 were alive, but moribund.
Figs 1 to 3 illustrate normal and affected digestive
tracts.
Clinical signs
Enlarged abdomen, apathy, no defaecation,
no milk
yield (the young are hungry and cold) and spontaneous death were observed.
Necropsy
The mammary glands had long nipples but no milk.
The lungs showed varying degrees of generalized
emphysema.
The stomach was slightly dilated and
filled with a watery fluid. In the small intestine the
proximal part showed a distinct distension with thin
watery contents which gradually
became thicker
along the length of the proximal small intestine until
it became a hard conical 'plug' leading to impaction
and ileus. The distal part of the small intestine was
either empty or contained 'faecal' pellets which are
totally misplaced in that part of the intestine. fn the
caecum the tail contained hard material whereas the
body was nearly empty or slightly filled with thin
contents. The large intestine was either empty or
filled with a few faecal pellets and occasionally with
mucous material.
6 females showed atypical findings: 2 cases had a
limited distension of the intestine (few centimetres);
2 cases had impaction with a 'plug' but no obvious
dilatation;
I case had a subnormal
filling of the
stomach and 1 case had an occlusion of the large,
rather than small, intestine.
Paresis of peristalsis
33
in lactating mice
Fig. I. The digestive tract of a normal healthy mouse.
Fig. 2. The digestive tract of a mouse which died as a result
of the disease. Note the slightly distended stomach and the
distinct distension of the proximal part of the small
intestine. In the distal part there is a segment with a hard
plug-like content (noted by forceps impressions). The
content in the 'tail' of the caecum has a similar (hard)
consistency. The distal part of the small intestine and the
large intestine are empty.
a
Fig. 3. Schematic drawings of the digestive tracts in healthy
(a) and affected (b) mice respectively. The degree of
distension of certain parts can be scen and the compactness
of gut contents is indicated by the darkness of the pattern.
34
Kunstyf
Histology
In 2 cases there was no inflammation
in any part of
the digestive tract, and with the exception of lung
emphysema,
no changes in heart, liver, spleen and
kidneys.
In 1 case there was oedema
of the
submucosa
of the ileum and some necrosis of
Peyer's patches.
Bacteriology
The organs were sterile and no pathogenic
were detected in the intestine.
microbes
Strain distribution
The distribution
of the syndrome
amongst
the
various strains reflected the number kept in the
Institute rather than any strain specificity. (C57BU
6J (20); DBA (10); C57BUKS
(9); AKR (3);
T-strain (2); Dwarf (2); C57BU"1 (I); not known
(3)). Information
on parity, litter size and day of
death after parturition
is given in Table 1.
Table l. Incidence of disease in relation to time after
parturition, parity and fecundity
Mean
(range)
±
SD
No. of
animals
evaluated
Time of death (days) 13·73 ± 4-44
after parturition
(8-25)
37
Number of litters
\·72 ± )·4
(1-6)
32
Number born
6·96 ± [·95
(5-11)
29
Discussion
The syndrome
described
here seems not to be
strain-specific
and is characterized
by a paralysis of
peristalsis, mainly in the proximal small intestine.
Impairment
of gut motility appears
to be the
primary cause and occlusion of the intestine (ileus)
is the most likely consequence.
The slightly enlarged
stomach with a watery content may be the result of
enhanced water intake.
Previous failure to recognize this syndrome by
researchers is probably due to its misinterpretation
as a post-mortem
change. In his lecture, Niissel
(1980) was the first to describe a high mortality in
lactating mice and he considered
it was due to
Clostridium
perfringens
enterotoxemia.
He was
most probably confronted with the same syndrome
described here together with a high bacterial load of
C/. perfril/gens,
and the toxins of this ubiquitous
micro-organism
may have aggravated
the symptoms. However, in contrast to his observation
of
diarrhoea
in the affected
females and/or their
young, we made no such observations.
The syndrome does not seem to be identical with
either the 'obturation
ileus' or the 'paralytical ileus'
described by Giittner & Karasek (1979). However,
it may be a combination
of both, i.e. a mechanical
occlu.sion by a plug-like impaction of the intestine
(obturation
ileus) together with a partial paralysis
(paralytical
ileus), the latter seeming
to be a
precondition
for the former. Organ changes in the
liver, spleen and lymph nodes accompanying
both
forms of paresis (Giittner & Karasek, 1979) were
not found in the present study. A recent published
handbook on the pathology of laboratory
animals
(McClure, Chapman,
Hooper, Smith & Fletcher,
1978) does not mention any similar condition.
Although in some strains of mice (Niissel, 1980)
and in some experiments
with mutagenicity testing
(Fahrig,
1983), the number of affected females
reached 30-40%, the syndrome seems to be sporadic having no obvious epidemiology.
In cases of
high mortality other complicating factors were most
probably involved and in agreement
with Niissel
(1980), the syndrome has never been observed in
males.
It is noticeable that an overwhelming
proportion
of females were affected during their first lactation
(Table I) and this finding coincides with those of
Niissel (1980) and Rapp, Kluge & Burow (1984). In
a study using 47 000 breeding
mice the latter
researchers observed a significantly higher mortality
during the first lactation - partly associated with
Citrobacter induced colitis (Deerberg,
1984). At this
stage the primiparous
mouse is lactating
after
parturition,
often simultaneously
pregnant
for a
second time, and yet not fully grown. We attribute
the disease to the failure to adapt to this physiological overload, in other words the disorder is due
to 'exhaustion'.
Similar health complications
are
well known in high-producing
female farm animals.
Our hypothesis is additionally supported by the lack
of any inflammation
or recovering any infectious
agent.
Exhaustion of the animals may well be linked to
calcium and its role in muscle contraction (Goldenberg & Meurer,
1983; Grover & Daniel, 1985).
Thus, an imbalance or severe exhaustion of calcium
reserves or other electrolytes,
as well as glucose
and/or
vitamin
E, may reduce
muscle
tone.
Subsequent
paralysis of peristalsis will ultimately
result in impaction and death. It was possible to
bleed and examine the serum of 2 female mice with
this syndrome. In addition to a high sodium level,
reduced levels of calcium and glucose were found. It
was not clear, however, if these changes could be
related to the syndrome or to terminal (agonal)
exhaustion. It is, likewise, unclear why the intestine
is the single target organ.
Shirley (1984) reported the increased nutritional
Paresis of peristalsis
35
in lactating mice
requirements
of lactating rats compared with pregnant rats and such requirements
may well hold for
mice too. Non-breeding
and breeding
mice are
usually fed 2 different kinds of standard diet. The
development
of a third supplemented
or enriched
diet for lactating breeding
mice might possibly
prevent the syndrome described.
Interestingly, we have observed similar changes in
3 non-lactating
females which had been given a
carcinogenic compound,
a polycyclic carbohydrate
2-acetylaminofluorene
(Fahrig,
1984), which directly impairs peristalsis. This finding suggests that a
pathologic condition similar to the syndrome described can be induced by toxic substances.
Acknowledgements
I am indebted to Mrs Dr Susanne
to Dr H. Ernst for the histological
Naumann and
examinations.
References
Dcerberg,
F. (1984). Personal communication.
Fahrig, R. (1981). Mutagenitiitsforschung
- ein Weg zur
Krebserkennung.
Die
Geschichte
der
Mutationsforschung bis zum Spot-Test.
Umschall in Wissenschaji
lind Technik 81. 529-533.
Fahrig, R. (1983). Personal communication.
Fahrig, R. (1984). Personal communication.
Goldenberg.
M. M. & Meurer, R. D. (1983). The effect of
calcium antagonists on contractions of the sensitized and
normal guinea pig ileum. Prm'wglandins 26, 615-622.
Grover. A. K. & Daniel. E. E. (eds) (1985). Calcillm and
Contractilitv. Smooth Mliscle. Clifton: Humana Press.
Giittner.
J. '& Karasek,
E. (1979). Einfrihrung in die
Versllchstierkunde, vol. 3. Versuehstierkrankheiten.
Jena: VEB G. Fischer.
KunstYr. I. (1983). Schwerpunkte
der bakteriologisehen
Ubcrwachung
von Versuchstierbestiinden.
In Schwer-
{JlInkte der Infektionsiibenvachung
bestiinden (ed. K. Bonath).
pp.
in
23-39.
VersllchstierBerlin &
Hamburg:
Parey.
Kunstyi" I., Matthiesen,
Th .. Giirtner, K., Maess, J. &
Heimann, W. (1982). Post-mating non-infectious
hydrometra in BALB/c:Bom
mice. Laboratory Animals 16,
51-55.
Parese der Peristaltik
McClure, H. M., Chapman, W. L.. Hooper, B. E .. Smith.
F. G. & Fletcher, O. J. (1978). The digestive systcm. In
Pathology of Laboratory Animals, vol. 1 (cds. K.
Bcnirschke,
F. M. Garner & 1'. C. Jones), pp. 17()-317.
New York. Heidelberg,
Berlin: Springer.
Niissel, M. (1980). C1ostridien-Enterotoxiimie
bei weiblichen Zuehtmiiusen.
Lecture during the 13th Scientific
Meeting of GV-SOLAS,
Lausanne
2R-30 May 1980.
Abstract.
Rapp, K. G., Kluge, R. & Burow. K. (1984). Zusammenhiinge
zwischen
bioehemisehen
Polymorphismen
und quantitativen
Merkmalen
bei Han:NMRI
Miiusen.
Hannover Colloqllillm of Laboratory Animal Science - a
lecture, Hannover
17 April 1984.
Shirley,
B. (1984). The food intake
of rats during
pregnancy and lactation. Laboratory Animal Science 34.
169-172.
Weber. A., Lembke. C. & Schiifer, R. (1982). Untersuchungen zum Vorkammen
von Campylobacter jejlllli
bei Kaninchen,
Meersehweinchen,
Ratten und Miiusen
in der Versuehtierhaltung.
Berliner lind Miinchener
Tieriirztliche Wochenschrift 95, 488-489.
und Ileus mit tOdlichem Ausgang bei laktierenden
Miiusen
I. KUNSTYR
Zusammenfassung
Auf der Grundlage
von Beobachtungen
an 45 spontan
gestorbenen
und 5 kranken Miiuseweibehen.
die wiihrend
zwei Jahren unterslicht
wurden, wird cine neue nosologisehe Einheit beschrieben:
die Parese der Peristaltik und
Ileus bei laktierenden
Miiusen. Das pathologisehe
Leitsymptom war dabei die Parese der Peristaltik mit sekundiirelll
Ileus,
lokalisiert
iiberwiegend
im Diinndarm.
Durchfall
wurde
nicht registriert,
die Entziindungskomponente
fehlte, es wurden keine infektii:isen Erreger
isoliert. Betroffen waren Miiusemiitter
von versehiedenen
Stiilllmen. Illeistens naeh dem ersten Wurf. iiberwiegend
am Ende der zweiten Laktationswoche.
Diese sporadisch
auftretende
Erkrankung
kann bis zu 40% Mortalitiit
verursaehen.
Es wird postuliert.
das Ersehi:ipfung - von
Calcium-Reserven,
Glukose,
usw. - die Ursache dieses
nicht-infektii:isen
pathologischen
Zustandcs ist. Endogene
(C1ostridien) oder exogene toxisehe Komponenten
kilnnen
vermutlich
diesen Zustand
versehlechtern,
bzw. seiber
herbeifiihren.
Um diesem pathologischcn
Zustand
vorzubeugen
wird
die
Entwicklung
eines
diiitctisehen
Zusatzes oder einer speziellen Diiit fiir laktierende
Miiusc
diskutiert
und el1lpfohlen.