The use of sodium lamps to brightly illuminate mouse houses during their dark phases

The human and murine diurnal rhythms are out of phase. Consequently in conventionally-lit mouse houses the mice's deep sleep is often disrupted, the daily welfare monitoring of the mice is limited by their inactivity, and scientific data obtained from the mice model the sleeping rather than awake human. Sodium light is bichromatic, with both wavelengths being in the human visual field but at the margin of murine vision. We report here that sodium lamps can be used to light mouse houses to a level that is comfortable for humans, but still sufficiently dull to permit nocturnal behaviour in mice. The response of mice to sodium light was initially monitored by recording the locomotory activity of BALB/c mice. The movement of mice in their cages greatly increased at the start of the nocturnal phase. Alterations in the white light cycle caused an acute change in the onset of nocturnal behaviour. In contrast, sodium light did not suppress the onset of nocturnal locomotory behaviour, even though the lighting was sufficiently bright for humans to read without light adaptation. The sodium lighting was then used to observe the nocturnal behaviour of over 150 mice of various strains, for over 1.5 years. Mice were invariably awake and alert during the nocturnal/sodium light phase. All exhibited high locomotory activity, except for nursing mothers. Some tasks, such as cage cleaning and minor surgery, were more easily done under white than sodium lighting. We therefore adjusted the timing of the light cycles to provide white light in the morning and sodium light (nocturnal phase) in the afternoon. This provided for easy operation of the mouse house, while yielding both animal welfare and scientific advantages.     

Proteolipids in the developing brains of normal mice and myelin deficient mutants

Abstract— A developmental study of proteolipids from brains of normal mice and two myelin deficient mutants, jimpy and quaking, was performed. The proteolipids were obtained by diethyl ether precipitation of washed total lipid extracts from whole brains and were analysed on polyacrylamide gels containing sodium dodecyl sulphate. The amount of ether precipitable material extractable from normal brains increased almost six-fold between 12 and 21 days posr partum. This increase was not observed with the mutant mice. Polyacrylamide gel electrophoretic analysis of the proteolipid fraction showed it to be heterogeneous, with eight major protein bands. Two of these proteins increased rapidly in quantity in normal mice between 13 and 21 days. These two proteins were present, in severely reduced quantities in the brains of jimpy and quaking mice at all ages examined. One of these proteolipids was the major species present in proteolipid extracts from the brains of normal mature mice. This protein coelectrophoresed with proteolipid isolated from purified myelin and has been tentatively identified as the myelin proteolipid. The other proteolipid which was deficient in jimpy and quaking brains was not characterized, but it appeared to be of extra-myelin origin, and suggests that parts of the brain other than the myelin sheath may be involved in the jimpy and quaking disorders.     

QUAKING MOUSE: ISOLATION AND CHARACTERIZATION OF MYELIN PROTEIN

A new technique, involving final purification on a continuous CsCl gradient, was utilized for the isolation of cerebral myelin from adult (4- to 6-month-old) quaking mice, littermate controls and young (10-day-old) normal mice. The yield of myelin from either adult quaking or normal young mice was 5-10 per cent of that from adult controls. After deli-pidation, myelin proteins were separated by polyacrylamide gel electrophoresis in buffers containing sodium dodecylsulphate. Two gel systems were utilized: (1) a high-resolution discontinuous electrophoresis system; and (2) a continuous system utilizing gels cross linked with ethylenediacrylate (EDA). The gels from the discontinuous system were stained with Fast Green and quantified by densitometry. The base lability of the EDA-linked gels permitted direct chemical determination of protein in specific bands. Myelin from brains of normal adult mice contained, as major components, one proteo-lipid and two basic proteins. There were also a number of high-molecular-weight proteins which represented a significant portion of the total. Myelin from quaking mice had qualitatively a similar distribution of proteins but the high-molecular-weight fraction comprised a much greater percentage of the total protein. The ratio of basic to proteolipid protein in preparations from quaking mice was considerably higher than that in the myelin from control mice. The distribution pattern of the myelin proteins from 10-day-old mice was quantitatively similar to that of quaking mice. Altogether the evidence supports the hypothesis that the quaking mutant provides a model of an immature nervous system with respect to myelination.     

Exposure to Strong Static Magnetic Fields Induces Hypoactivity in Weaning Mice

We studied the effects of a prolongued exposure to a strong (1.0 Tesla) static and uniform magnetic field upon the open field behaviour and body weight of weaning mice. We observed a marked reduction in the exploratory activity of mice exposed to the field relative to that of control animals kept in similar surroundings, and handled in the same way as the exposed mice. One week of continuous exposure to a 1.0 T field significantly reduces peripheral square entries (p<0.01) as well as rearings (p<0.05), but has no effect on body weight. Our findings agree with the suggestion that a strong magnetic field may act as stressing agent.     

Myelin-Associated Glycoprotein in the Central and Peripheral Nervous System of Quaking Mice

The myelin-associated glycoprotein (MAG) was quantitated in the CNS and PNS of quaking mice and the levels compared to the levels of myelin basic protein (MBP) and 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) activity. In the brainstems of 36-day-old quaking mice, MBP, MAG, and CNPase were reduced to 12, 16, and 29% of control levels, respectively. In the sciatic nerves of the 36-day-old quaking mice, MBP and CNPase were 38 and 75% of control levels, respectively, whereas the concentration of MAG was unchanged or slightly increased. Similar quantitative results were obtained for the sciatic nerves and spinal roots of 7-month-old quaking mice. Immunoblots showed that the principal MAG band from the brainstems, sciatic nerves, and spinal roots of the quaking mice had a higher than normal apparent Mr. In addition, there was a minor component reacting with anti-MAG antiserum in the brainstems of the quaking mice that had a slightly lower Mr than control MAG and was not detected in the normal mice. The results for the quaking mice are compared with those from similar studies on other mutants with dysmyelination of the CNS and PNS.     

Albinism and mouse behaviour

This study examines the behavioural effects of the gene for albinism (c-locus) in mice. For this purpose, homozygous albino mutants were compared with heterozygous pigmented mice, all males, in three experimental situations: 1. In order to obtain a general picture of the behavioural phenotype, the frequencies of 22 acts and postures displayed by solitary mice in a large observation cage were observed directly. 2. Using a platform that could be fixed at different heights, the levels and latencies of descent were recorded for the two genotypes. 3. In a pole-climbing test, the climbing latencies of the animals were measured. These experiments indicated that albinos show more fear of heights (are more acrophobic) than wild-type mice. Their visual exploration of space appears to be about normal. The problem of the causation of this acrophobia is discussed.In one single respect (climbing latency) the mutants turned out to be more variable than the controls, a finding which might be explained in terms of a weaker canalization of their phenotype.     

Alpha hydroxylation of lignoceric acid to cerebronic acid during brain development. Diminished hydroxylase activity in myelin-deficient mouse mutants.

Alpha Hydroxylation of lignoceric acid (n-tetracosanoic acid) to cerebronic acid (2-hydroxylignoceric acid) by postnuclear preparations of brains from developing rat, mouse, and several neurological mouse mutants was studied. The preparations of brains from jimpy and myelin synthesis deficiency (msd) mice were found to synthesize cerebronic acid at less than 10 percent of their control rates, and those from quaking and dilute-lethal approximately 30 and 50 percent, respectively. The apparent low rate of in vitro hydroxylation by brains of the mutant mice appeared to be due to decreased synthesis rather than increased oxidation of cerebronic acid. Mixing experiments eliminated the possibility of an inhibitor in the mutant or an activator in normal animals. The preparations of brains from wabbler-lethal, ducky, and weaver mice showed normal activity. The developmental pattern of the hydroxylase activity was examined in quaking, jimpy, and their control mice. In normal brains the hydroxylase activity was low in the immediate postnatal period, increased sharply between 10 and 20 days after birth, and fell to a low level following maturation of the brain. The hydroxylase activity in quaking mice changed similarly during brain development but at a much reduced level. The brains of jimpy mice had barely detectable hydroxylase activity which changed little with age and reached a peak at about 15 days postpartum. The subnormal hydroxylase activity in brains of quaking mice and the near absence in brains of jimpy and msd mice correlate with the observations that myelin deficiency is more severe in jimpy and msd than in quaking. These results suggest a close association of the synthesis of cerebronic acid with the synthesis of the characteristic myelin lipid that is cerebroside (N-acyl sphingosine beta-D-galactoside).     

Neuronal expression of mutations affecting primarily glia in the mouse: studies in the dysmyelinated and convulsive mutant quaking

1. Various aspects of the noradrenergic system in the brain of the dysmyelinating convulsive mutant mice quaking have been examined. 2. Determination of the endogenous contents of noradrenaline and its metabolite 3-methoxy 4-hydroxyphenyl-ethyleneglycol (MOPEG), as well as measurement of the electrically-evoked release of (3H)-noradrenaline shows an increased noradrenergic activity in the brain of the mutants, when compared to non convulsive controls of the same strain. 3. Ontogenic development of alpha adrenergic receptors indicate that an increased density of alpha-2 sites precedes the appearance of the first convulsions by approximately one week. 4. Anatomical determination of the number of noradrenergic neuronal cell bodies in the locus coeruleus shows a hyperplasia of this nucleus in the mutants. 5. Electrolytic coagulation of the locus coeruleus inhibits the convulsions of the quaking mice. 6. These results suggest that an alteration of the embryonic differentiation of the locus coeruleus, which gives rise to the majority of brain noradrenergic neurons, provokes a hyperactivity of this neuronal system, thereby triggering the convulsions of the quaking mutant mice. 7. The possible involvement of other neurotransmitter systems in the convulsions of these mutants, together with the nature of the relationship between neuronal abnormalities and dysmyelination phenomenon, are discussed.     

Studies of brain myelin in the "quaking mouse"

Myelin was isolated from the brains of "quaking" and littermate control animals and its composition was determined. The brains of quaking animals contained approximately one-fourth as much myelin as the control animals. There were qualitative as well as quantitative differences between the myelin from the two groups. By continuous cesium chloride gradient flotation it was shown that the myelin from the quaking animals consisted solely of a band corresponding to the heavier and smaller of the two bands found in normal controls. Cholesterol and glycolipids were lower and phospholipids (mainly phosphatidylcholine) and protein were higher in quaking animals than in controls. Also, phosphatidal-ethanolamine was decreased, and several consistent differences in the fatty acids (both unsubstituted and hydroxy) and aldehydes of the component lipids were found. In general there were smaller amounts of monounsaturated fatty acids in quaking animals. We suggest from these findings that myelin in the quaking mouse has certain compositional similarities with juvenile myelin, but it may be an abnormal type of myelin.     

A spin-label study of sciatic nerves from quaking, jimpy and trembler mice.

The spin labels, 5-nitroxide stearic acid and 16-nitroxide stearic acid were incorporated into whole sciatic nerves dissected from normal, quaking, jimpy and trembler mice. With 5-nitroxide stearic acid, we have studied the thermal variation of the maximal apparent coupling constant (T) between 0 degrees C and 50 degrees C. Within this range of temperatures, we obtained identical values of 2 T for nerves from normal and jimpy mice, whereas 2 T was smaller for nerves from quaking and trembler mice. With 16-nitroxide stearic acid, composite spectra were recorded, particularly in the high-field range. A line characteristic of myelin was clearly observed in the spectra of nerves from normal and jimpy mice; its intensity was somewhat less in nerves from quaking mice and much less in spectra from trembler mice. A shoulder in the principal highfield line of the spectrum is modified only with nerves from jimpy mice. The results agree well with those obtained by electron microscopy, which reveal normal myelination in nerves from jimpy mice, a slight modification of the myelin from those of quaking mice and a practically complete demyelination in peripheral nerves from trembler mice. However, the structure of the nerves of jimpy mice also seems to be modified at an, as yet, undetermined level.     

In vitro acylation of myelin PLP and DM-20 in the quaking mouse brain

Both proteolipid proteins (PLP) and DM-20 were found to be present by the immunoblot technique in myelin isolated from quaking mouse brain; however, the relative concentration of these proteins in myelin from quaking brain was substantially reduced when compared to the control. Brain slices from littermate control and quaking mice were incubated with [³H]palmitic acid to determine the incorporation of fatty acid into myelin proteolipid proteins. Fluorography of gels containing myelin proteins from control and quaking mice brain revealed that both PLP and DM-20 were acylated. The incorporation of [³H]palmitic acid into quaking myelin PLP and DM-20 was reduced by 75% and 20% respectively of those in control brain. The significance of differential acylation of quaking myelin PLP and DM-20 is discussed with respect to availability of non-acylated pools of proteolipid proteins and the activities of acylating enzymes.     

Relationship between the sequelae of zoosocial isolation and individual characteristics of the animal

The changes were studied of various psychophysiological characteristics of mice behaviour, arising after prolonged solitary isolation in cages. The qualitative specificity of such changes is non-uniform and depends on the animals' individual characteristics (spontaneously aggressive or nonaggressive after isolation). Two types of the consequences of isolation are singled out: 1) General changes (non-specific) arising in all groups of mice; 2) Special changes (specific), typical of a certain group of animals only. In the group of aggressive mice there is a difference between aggression enhanced by isolation, and that which developed in the course of isolation. The most substantial qualitative changes in behaviour takes place in the latter case. It has been suggested that only individual approach makes it possible to determine exactly the qualitative aspects of social isolation consequences.     

Etude “in vitro” des acides gras synthétisés dans les microsomes de cerveaux de souris normales et “quaking”

Radiogas chromatographic studies of the products of fatty acid biosynthesis in mice brain microsomes confirm the existence of a «de novo system from acetyl-CoA and malonyl-CoA and of a least two elongating systems for long chain fatty acids, involving malonyl-CoA. The possibility of an intermediary system leading from C₁₈ to C₂₀ fatty acids has been evoked.Comparison between non mutant and quaking mice indicates that all the microsomal fatty acid biosynthetic systems are depressed. The biosynthetic system elongating fatty acids from C₁₈ is the one which is the most modified quantitatively and qualitatively in quaking. Microsomal and soluble «de novo systems are qualitatively intact.     

Genetic correlation between resting metabolic rate and exploratory behaviour in deer mice (Peromyscus maniculatus)

According to the 'pace-of-life' syndrome hypothesis, differences in resting metabolic rate (RMR) should be genetically associated with exploratory behaviour. A large number of studies reported significant heritability for both RMR and exploratory behaviour, but the genetic correlation between the two has yet to be documented. We used a quantitative genetic approach to decompose the phenotypic (co)variance of several metabolic and behavioural measures into components of additive genetic, common environment and permanent environment variance in captive deer mice. We found significant additive genetic variance for two mass-independent metabolic measures (RMR and the average metabolic rate throughout the respirometry run) and two behavioural measures (time spent in centre and distance moved in a novel environment). We also detected positive additive genetic correlation between mass-independent RMR and distance moved (r(A) = 0.78 ± 0.23). Our results suggest that RMR and exploratory behaviour are functionally integrated traits in deer mice, providing empirical support for one of the connections within the pace-of-life syndrome hypothesis.     

Functional Analysis of Mutations of Murine Chromosome 17 with the Use of Tertiary Trisomy

Analysis of the functional nature of mutations can be based on comparisons of their manifestation in organisms with a deletion or duplication of a particular chromosome segment. With the use of reciprocal translocation T(16;17)43H, it is feasible to produce mice with tertiary trisomy of the proximal region of chromosome 17. The mutations on chromosome 17 we tested included brachyury (T), hairpin tail (Thp), kinky (Fuki), quaking (qk), tufted (tf), as well as tct (t complex tail interaction), and tcl (t complex lethal) that are specific to t haplotypes. The set of dominant and recessive mutations was assigned to two groups: one obligatory, manifesting itself in the phenotype independently of the number of normal alleles in di- and trisomics, and the other facultative, phenotypically manifesting itself depending upon the dosage of mutant alleles. A model was derived from analysis of the interaction of the T and Thp mutations with t haplotypes. It seeks to explain the morphogenetic effects of the mutations observed in mice of different genotypes. The tir gene is postulated to reside on chromosome 17 within its framework. It is suggested that the gene dosage ratio at the tir and tct loci determines tail length.     

Functional analysis of mutations on murine chromosome 17 using tertiary trisomy

Analysis of the functional nature of mutations can be based on their manifestation in organisms with a deletion or a duplication of a particular chromosome segment. With the use of reciprocal translocation T(16;17)43H it is feasible to produce mice with tertiary trisomy for proximal region of chromosome 17. The mutations on chromosome 17 we tested included brachyury (T), hairpin tail (Thp), kinky (Fuki), quaking (qk), tufted (tf), as well as tct (t-complex tail interaction) and tcl (t complex lethal), that are specific for t haplotypes. The set of dominant and recessive mutations was assigned to two groups, one obligatory manifesting itself in the phenotype independently of the number of normal alleles in di- and trisomics, and the other facultative, phenotypically manifesting itself, depending upon the dosage of mutant alleles. A model was derived from analysis of the interaction of the T and Thp mutations with t haplotypes which is to explain the morphogenetic effects of the mutations observed in mice of different genotypes. The tir gene is postulated to reside on chromosome 17 within its framework. It is suggested that the gene dosage ratio at the tir and tct loci determines tail length.     

Photoacoustic studies of non-radiative relaxation of excited states in melanin

Photoacoustic measurements made at various chopping frequencies on dense acqueous melanin suspensions have revealed a significant dependence upon pH and redox state. It is shown that such behaviour, differing from the simple predictions of the Rosencwaig-Gersho theory, can be explained in terms of finite carrier diffusion and recombination times. The implications of these findings with respect to the amorphous semiconductor model proposed to describe the dynamic role of epidermal melanin are discussed. From the experimental data, values of physical parameters were calculated which allow a qualitative correlation between chemical states and electronic behaviour and, consequently, some aspects of the molecular biology of the melanosome, founded on a rigorous base.     

Behaviour of the yellow-eyed penguin chick

The ontogeny of yellow-eyed penguin ( Megadyptes antipodes ) chick behaviour follows the order of development determined by Nice (1962) for several species of birds, and by Spurr (1975) for the Adélie penguin ( Pygoscelis adeliae ). Feeding and comfort behaviours are the first to develop, followed by locomotion and aggressive behaviour.
Active solicitation of food may occur at one day of age. Chicks initially use non-visual cues to mediate begging. After their eyes open on the third or fourth day there is an increase in the use of visual stimuli, and begging occurs most often following adult nest relief. Sibling rivalry is not intense, occurring least during feeding, and in general both chicks are fed at each session.
The chicks are brooded for the first 21–25 days. At sparsely vegetated nest sites overheating may occur after 21 days and down-covered chicks will seek shade and pant in hot weather.
Throughout the 6–7 weeks of the guard phase there is a decrease in the amount of time spent resting in a prone posture, and an increase in exploratory, locomotory behaviour. During the post-guard phase, and until fledging and independence at 15 weeks after hatching, chicks may wander up to 20 m from the nest bowl during exploration, shade-seeking and feeding.
Adults feed only their own chicks, and chicks appear to beg only from their parents. Dense vegetation and long distances between nests tend to restrict contact between adults and chicks from neighbouring nests, and prevent the formation of large chick crèches.     

Hyperactive behaviour in the mouse model of mucopolysaccharidosis IIIB in the open field and home cage environments

Mucopolysaccharidosis IIIB (MPS IIIB) is a lysosomal storage disorder characterized by severe behavioural disturbances and progressive loss of cognitive and motor function. There is no effective treatment, but behavioural testing is a valuable tool to assess neurodegeneration and the effect of novel therapies in mouse models of disease. Several groups have evaluated behaviour in this model, but the data are inconsistent, often conflicting with patient natural history. We hypothesize that this discrepancy could be due to differences in open field habituation and home cage behaviour. Eight-month-old wild-type and MPS IIIB mice were tested in a 1-h open field test, performed 1.5 h after lights on, and a 24-h home cage behaviour test performed after 24 h of acclimatization. In the 1-h test, MPS IIIB mice were hyperactive, with increased rapid exploratory behaviour and reduced immobility time. No differences in anxiety were seen. Over the course of the test, differences became more pronounced with maximal effects at 1 h. The 24-hour home cage test was less reliable. There was evidence of increased hyperactivity in MPS IIIB mice, however, immobility was also increased, suggesting a level of inconsistency in this test. Performance of open field analysis within 1-2 h after lights on is probably critical to achieving maximal success as MPS IIIB mice have a peak in activity around this time. The open field test effectively identifies hyperactive behaviour in MPS IIIB mice and is a significant tool for evaluating effects of therapy on neurodegeneration.     

Behaviour of laboratory mice in different housing conditions when allowed to self-administer an anxiolytic

Standard cages prevent mice from performing several natural behaviours for which they are motivated. As a consequence, abnormal behaviours sometimes develop and mice often spend long periods inactive. To improve welfare, cages are sometimes furnished with items such as nesting material, shelters and running wheels. We have previously reported that when allowed to self-administer an anxiolytic, mice in furnished cages consume less anxiolytic than mice in standard cages. This paper presents the results of behaviour studies of the mice in the same experiment. Female C57BL/6J mice (3 per cage) were housed in Standard (n = 10), Unpredictable (n = 10) or Furnished (n = 6) cages. Unpredictable cages were identical to Standard cages, but were exposed to unpredictable events two to three times a week. Furnished cages were double the size of Standard cages and contained nesting material, nest box, tubes, chew blocks and a running wheel. During three consecutive periods, mice had access to only water (control), water or an anxiolytic solution on a daily alternating schedule (forced consumption), and finally, both water and anxiolytic (self-administration). Behaviour was analysed from video recordings taken during the dark phase. The housing type affected behaviour both under the control and the self-administration conditions. Overall, mice in Furnished cages spent less time resting and performing bar-related behaviours and more time on exploratory/locomotory behaviours. Mice in Furnished cages also performed less bar-circling stereotypies than mice in Standard cages. The Unpredictable treatment did not significantly affect behaviour compared to mice in the Standard conditions. There was an overall effect of anxiolytic availability on rest-related behaviours and on exploration-locomotion behaviours, in that mice rested more and spent less time on exploration and locomotion when they were able to self-administer the anxiolytic.