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Early behavioral development of mice is affected by staggerer mutation as soon as postnatal day three
Developmental Brain Research 101 Ž1997. 81–84
Research report
Early behavioral development of mice is affected by staggerer mutation as soon as postnatal day three Patricia Heuze, ´ Christophe Feron ´ ) , Claude Baudoin LEEC, Laboratoire d’Ethologie Experimentale et Comparee, ´ ´ URA CNRS 2214, UniÕersite´ Paris Nord, 93430 Villetaneuse, France Accepted 25 February 1997
Abstract Staggerer is a neurological mutation of mice that affects the development of the central nervous system and causes abnormal behaviors. The staggerer cerebellum is already abnormal at birth and as the animal grows up there is a progressive loss of granule cells which have all disappeared by day 28. The earliest behavioral disturbance observed is a motor deficiency which occurs between 10 and 15 days – i.e. several days later than the appearance of the cortical abnormalities. To show that staggerer mutant mice also differ from normal mice in behavioral aspects before the age of 10 days, 28 staggerer pups and 246 normal pups aged from 1 to 9 days underwent different motor tests. In addition, the number of ultrasounds emitted during 40 s was recorded, and the animals were weighed every day. Differences between staggerer and normal mice were found as early as 3 days: staggerers were less efficient in motor tasks and they weighed less than normal mice. Staggerers also differed from normal mice in ultrasound production. Keywords: Neurological staggerer mutation; C57BLr6 mouse; Development; Body weight; Motor ability; Ultrasound
1. Introduction Staggerer mutation is a neurological and recessive mutation affecting the development of the central nervous system ŽCNS. and inducing abnormal behavior. The cerebellum is the principal cortical structure of the CNS affected. At birth, the mutant’s external granular layer is thinner than in normal mice, and from day 3, it becomes even thinner and there are fewer postmitotic granule cell neurons. The Purkinje cells are stunted, with greatly reduced arborization, and they are scattered throughout the cortical region w7x. Granule cells form only primitive junctions with the Purkinje cell dendritic shafts and are not superseded by mature junctions at 7 days as in normal mice. As a consequence, the staggerer’s parallel fibers start to degenerate and at 10 days the body cells begin to degenerate. At 28 days, all granule cells have disappeared. Finally, the cerebellum is only one third normal size and the normally distinct lamination of the cortex is disturbed w8x. In addition, between birth and 10 days, 40% of the neurons of the inferior olivary nucleus, connected to Purkinje cells, also degenerate w12x. The earliest behavioral disturbances induced by the )
Corresponding author. Fax: q33 Ž1. 49403975.
abnormal maturation of the cerebellum are observed only between the 10th and the 15th day after birth. The animal’s locomotion is poorly coordinated, and there is lurching motion that provokes frequent falls. Later, other abnormal aspects of behavior can be observed. For example, when a staggerer is placed in a new environment or in presence of an unknown object it shows no neophobic behavior as does a normal mouse w9x. Furthermore, adult staggerer males never demonstrate sexual behavior, probably because of olfactory deficiency w2x, and staggerer females rarely engage in maternal behavior w3x. Regarding the early abnormalities of the staggerer’s cerebellum, we can expect to observe behavioral abnormalities earlier than 10 days. In our study, pups aged from 1 to 9 days are placed in different situations involving motor responses that are evaluated. We also study two characteristics of the developing mouse: ponderal evolution and ultrasound production. 2. Materials and methods Staggerer mice pups Žsgrsg. and non-mutant pups Žqrsg, qrq . are produced with C57BLr6 mice heterozygous for the mutation. Heterozygous Žqrsg. and homozygous Žqrq . pups are not distinguished in the
0165-3806r97r$17.00 Copyright q 1997 Elsevier Science B.V. All rights reserved. PII S 0 1 6 5 - 3 8 0 6 Ž 9 7 . 0 0 0 4 9 - 7
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P. Heuze´ et al.r DeÕelopmental Brain Research 101 (1997) 81–84
non-mutant group as no study shows neurological differences between these two genotypes before the animals are one year old w13x. Pregnant females are isolated in 31 = 19.5 = 12 cm cages, containing 1.5 g of cotton for nest building. The room temperature is between 22 and 268C and the photoperiod is 12 h light and 12 hours dark, the light being switched on at 7:00 a.m. Each pup is individually identified with colored ink on the claws. The pups are weighed between 9:30 and 11:30 h every day. At the same time, they undergo a ‘righting’ test, that is, the animal is placed on its back which produces an increase of motor activity that generally leads to a recovery of normal position Žwith all four feet on the ground.. The time taken by the animal to recover is recorded with a maximum time of 2 min. On days 3, 5, 7 and 9, a cliff drop aversion test is made between 14:00 and 18:00 h, and on days 2, 4, 6 and 8, a quantification of ultrasounds is made, also between 14:00 and 18:00 h. In the cliff drop aversion test, the pup is placed on the edge of a platform Žwhich is 16 cm high. with its forepaws and face over the edge. The animal will turn and crawl away from the cliff drop. The turn-away time is noted, as well as any fall off the platform. The emission of ultrasounds is obtained by suspending the pup by the tail 40 s. The ultrasounds are conveyed into audible signals by an S25 Bat Detector, so that the experimentator can note the number of ultrasounds emitted. In the study, 274 pups were tested and 28 were mutants. For practical reasons, the composition and the size of the groups differed at each age. On the entire period studied, the number of mutants composing a group Žnoted NŽsg.. varied from 8 to 27 and the number of non-mutants ŽNŽn.. from 24 to 56. Consequently, no longitudinal study was possible and data concerning staggerers and non-staggerers were compared age by age, using the t-test for quantitative data and using x 2 or the Fisher exact probability test Ždepending on the size of the groups. for qualitative data. 3. Results
Fig. 2. Righting test: mean time to regain normal position and standard error. ) ) P - 0.03, ) ) ) P - 0.01.
ŽNŽsg. s 16, NŽn. s 35, t s y2.1, P - 0.05., day 4 ŽNŽsg. s 17, NŽn. s 36, t s y2.6, P - 0.03., day 6 ŽNŽsg. s 18, NŽn. s 41, t s y2.1, P - 0.05. and day 8 ŽNŽsg. s 20, NŽn. s 54, t s y2.6, P - 0.03.. 3.2. Righting test In both groups, some animals did not succeed in righting themselves in 2 min until day 6, but there are no significant differences Žat day 2, 2% of non-mutants did not succeed in 2 min versus 40% in mutants; at day 3, 2% of non-mutants failed versus 25%; at day 4, 12% of non-mutants failed versus 33%; at day 5, 3% of nonmutants failed versus 1% and at day 6, 4% of non-mutants failed versus 2%.. Considering those that did succeed in 2 min, the mutants are usually less efficient than non-mutants; they take more time to right themselves, especially on day 3 ŽNŽsg. s 15, NŽn. s 32, t s 2.9, P - 0.01., day 7 ŽNŽsg. s 19, NŽn. s 56, t s 2.3, P - 0.03., day 8 ŽNŽsg. s 27, NŽn. s 54, t s 2.6, P - 0.03. and day 9 ŽNŽsg. s 22, NŽn. s 50, t s 3.1, P - 0.01. ŽFig. 2.. 3.3. Cliff drop aÕersion test There is no difference between the two groups in terms of time taken to turn away from the cliff. But, as shown in
3.1. Weight The mutant’s weight is lower during the entire period studied ŽFig. 1., with significant differences on day 3
Fig. 1. Evolution of weight from 2 to 9 days, mean values and standard error, ) P - 0.05, ) ) P - 0.03.
Fig. 3. Cliff drop aversion test: proportion of animals falling off the cliff. The fractions indicate how many of all animals tested fell. ) ) P - 0.03, ))) P - 0.01. At day 3, x 2 s 7.76, P s 0.005, day 5, Fisher’s test, P s 0.08, day 7, x 2 s6.75, P s 0.009, day 9, Fisher’s test, P s 0.06.
P. Heuze´ et al.r DeÕelopmental Brain Research 101 (1997) 81–84
Fig. 4. Number of ultrasonic vocalisations, mean values and standard error, ) ) P - 0.03.
Fig. 3, the proportion of animals falling off the cliff is more important in the staggerer group. 3.4. Ultrasounds Staggerers emit more ultrasounds than normal mice at 6 days ŽNŽsg. s 9, NŽn. s 19, t s 2.6, P - 0.03. and 8 days ŽNŽsg. s 16, NŽn. s 38, t s 2.4, P - 0.03.. In fact, the number of ultrasounds in normal mice decreases between day 4 and 6, with staggerers, it decreases between day 6 and 8 ŽFig. 4..
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staggerers, thermoregulation processes could be initiated a couple of days later, and as a result, they emit more ultrasounds than normal mice when isolated from the nest – i.e. source of heat – at 6 and 8 days. In conclusion, our study shows the existence of behavioral and physical Ži.e. weight. deficiencies in staggerer as early as the third day of age. Furthermore, from 6 to 9 days of age, it is clear that the staggerers differ from the non-mutants in weight, time taken to right themselves, capacity to avoid falling from the cliff and quantity of ultrasounds emitted. In the adult staggerer, both weight loss and motor deficiency are maintained. But it is possible to improve staggerer motor performance by placing the animal in a special set-up that stimulates its vestibular system w6x. Some of the socially abnormal behavior described in the Introduction can also be partly overcome. For example, a male staggerer may exhibit sexual behavior toward a receptive female when reared from the age of 40 days with several normal females w5x. In other words, particular post-weaning social environments can provoke behavior that is absent because of mutation. The environment being an active factor of the behavioral development of the staggerer mutant, it would be interesting to investigate the influence of pre-weaning special environments on staggerers identified few days after birth.
Acknowledgements 4. Discussion The aim of this study was to distinguish mutants from non-mutants before the age of 9 days, by using behavioral and physical tests. Differences were found as early as the third day of life in all the motor tests used. Staggerers weighed less during the entire period. This mutant characteristic is maintained as the animal grows up; the difference of weight has already been shown in juvenile staggerer of 40 days old w4x. During the righting tests, there was a significant difference in performance at day three but not the day immediately following. Pups from 1 to 4 days did not appear to coordinate their movements correctly in righting themselves w1x and there was an important interindividual variation in the time taken to regain normal position. On the other hand, on days 7, 8 and 9, it was clear that non-mutants always succeeded easily in righting themselves. The mutants also succeeded, but not as quickly and easily. In the cliff drop aversion tests, all animals attempted to recoil in order to avoid falling but the staggerers were less efficient and the proportion of pups that fell over the cliff was greater in mutants. Regarding ultrasound production, it is well known that the number of calls with normal mice increases until 4 or 5 days of age, then decreases until about 15 days of age and the lowering of the calls at 5 days is correlated with the beginning of homeothermal development w10,11x. In
We thank Simone Demouron for taking care of the mutants, Bob Flyn for his help in writing the manuscript and Gerard Martin for his comments and technical support. ´
References w1x J. Altman, K. Sudarshan, Postnatal development of locomotion in the laboratory rat, Anim. Behav. 23 Ž1975. 893–920. w2x C. Baudoin, C. Feron, V. Deiss, Olfactory deficit induced by the ´ murine staggerer mutation: behavioural data, in: R. Apfelbach, D. Muller-Schwarze, K. Reutter, E. Weiler ŽEds.., Chemical Signals in ¨ Vertebrates VII, Advances in the Biosciences, vol. 93, Pergamon Elsevier, 1994, 413–419. w3x S. Boufares, J.M. Guastavino, K. Larsson, Restoration of staggerer mouse maternal behavior following long term breeding selection, Physiol. Behav. 53 Ž1993. 1151–1155. w4x C. Feron, Les comportements socio-sexuels des souris staggerer ´ males: caracteristiques et effets de l’experience sociale. These ˆ ´ ´ ` d’Universite. ´ Universite´ Paris XIII, 1992, 181 pp. w5x C. Feron, C. Baudoin, M.S. Magnusson, Effect of post-weaning ´ social experience with normal female on the behaviour of adult male staggerer mice interacting with normal females, Behav. Process. 23 Ž1991. 142–152. w6x G. Goodall, J.M. Guastavino, C. Feron, Adaptation and behavioural ´ plasticity: an investigation of a neurological mutant mouse, in: V. Leonovicovd, V.J.A. Novak ŽEds.., Behaviour as One of the Main Factor of Evolution, Czechoslovak Academy Sciences Praha, 1987, 173–192.
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P. Heuze´ et al.r DeÕelopmental Brain Research 101 (1997) 81–84
w7x K. Herrup, Role of staggerer gene in determining cell number in cerebellar cortex I. Granule cell death is an indirect consequence of staggerer gene action, Dev. Brain Res. 11 Ž1983. 267–274. w8x D.M.D. Landis, R.L. Sidman, Electron microscopic analysis of postnatal histogenesis in the cerebellar cortex of staggerer mutant mice, J. Comp. Neurol. 179 Ž1978. 831–864. w9x R. Misslin, M. Cigrang, J.M. Guastavino, Responses to novelty in staggerer mutant mice, Behav. Process. 12 Ž1986. 51–56. w10x E. Noirot, D. Pye, Sound analysis of ultrasonic distress calls of mouse pups as a function of their age, Anim. Behav. 17 Ž1969. 340–349.
w11x E. Okon, Factors affecting ultrasound production in infant rodents, J. Zool. London 168 Ž1972. 139–148. w12x H. Zanjani, N. Delhaye-Bouchaud, J. Mariani, Decreased number of cells in the inferior olivary nucleus of the developing staggerer mouse, Dev. Brain Res. 21 Ž1985. 141–146. w13x H. Zanjani, N. Delhaye-Bouchaud, J. Mariani, K. Herrup, Neuronal cell loss in heterozygous staggerer mutant mice: a model for genetic contributions to the aging process, Dev. Brain Res. 67 Ž1991. 153–160.
Research report
Early behavioral development of mice is affected by staggerer mutation as soon as postnatal day three Patricia Heuze, ´ Christophe Feron ´ ) , Claude Baudoin LEEC, Laboratoire d’Ethologie Experimentale et Comparee, ´ ´ URA CNRS 2214, UniÕersite´ Paris Nord, 93430 Villetaneuse, France Accepted 25 February 1997
Abstract Staggerer is a neurological mutation of mice that affects the development of the central nervous system and causes abnormal behaviors. The staggerer cerebellum is already abnormal at birth and as the animal grows up there is a progressive loss of granule cells which have all disappeared by day 28. The earliest behavioral disturbance observed is a motor deficiency which occurs between 10 and 15 days – i.e. several days later than the appearance of the cortical abnormalities. To show that staggerer mutant mice also differ from normal mice in behavioral aspects before the age of 10 days, 28 staggerer pups and 246 normal pups aged from 1 to 9 days underwent different motor tests. In addition, the number of ultrasounds emitted during 40 s was recorded, and the animals were weighed every day. Differences between staggerer and normal mice were found as early as 3 days: staggerers were less efficient in motor tasks and they weighed less than normal mice. Staggerers also differed from normal mice in ultrasound production. Keywords: Neurological staggerer mutation; C57BLr6 mouse; Development; Body weight; Motor ability; Ultrasound
1. Introduction Staggerer mutation is a neurological and recessive mutation affecting the development of the central nervous system ŽCNS. and inducing abnormal behavior. The cerebellum is the principal cortical structure of the CNS affected. At birth, the mutant’s external granular layer is thinner than in normal mice, and from day 3, it becomes even thinner and there are fewer postmitotic granule cell neurons. The Purkinje cells are stunted, with greatly reduced arborization, and they are scattered throughout the cortical region w7x. Granule cells form only primitive junctions with the Purkinje cell dendritic shafts and are not superseded by mature junctions at 7 days as in normal mice. As a consequence, the staggerer’s parallel fibers start to degenerate and at 10 days the body cells begin to degenerate. At 28 days, all granule cells have disappeared. Finally, the cerebellum is only one third normal size and the normally distinct lamination of the cortex is disturbed w8x. In addition, between birth and 10 days, 40% of the neurons of the inferior olivary nucleus, connected to Purkinje cells, also degenerate w12x. The earliest behavioral disturbances induced by the )
Corresponding author. Fax: q33 Ž1. 49403975.
abnormal maturation of the cerebellum are observed only between the 10th and the 15th day after birth. The animal’s locomotion is poorly coordinated, and there is lurching motion that provokes frequent falls. Later, other abnormal aspects of behavior can be observed. For example, when a staggerer is placed in a new environment or in presence of an unknown object it shows no neophobic behavior as does a normal mouse w9x. Furthermore, adult staggerer males never demonstrate sexual behavior, probably because of olfactory deficiency w2x, and staggerer females rarely engage in maternal behavior w3x. Regarding the early abnormalities of the staggerer’s cerebellum, we can expect to observe behavioral abnormalities earlier than 10 days. In our study, pups aged from 1 to 9 days are placed in different situations involving motor responses that are evaluated. We also study two characteristics of the developing mouse: ponderal evolution and ultrasound production. 2. Materials and methods Staggerer mice pups Žsgrsg. and non-mutant pups Žqrsg, qrq . are produced with C57BLr6 mice heterozygous for the mutation. Heterozygous Žqrsg. and homozygous Žqrq . pups are not distinguished in the
0165-3806r97r$17.00 Copyright q 1997 Elsevier Science B.V. All rights reserved. PII S 0 1 6 5 - 3 8 0 6 Ž 9 7 . 0 0 0 4 9 - 7
82
P. Heuze´ et al.r DeÕelopmental Brain Research 101 (1997) 81–84
non-mutant group as no study shows neurological differences between these two genotypes before the animals are one year old w13x. Pregnant females are isolated in 31 = 19.5 = 12 cm cages, containing 1.5 g of cotton for nest building. The room temperature is between 22 and 268C and the photoperiod is 12 h light and 12 hours dark, the light being switched on at 7:00 a.m. Each pup is individually identified with colored ink on the claws. The pups are weighed between 9:30 and 11:30 h every day. At the same time, they undergo a ‘righting’ test, that is, the animal is placed on its back which produces an increase of motor activity that generally leads to a recovery of normal position Žwith all four feet on the ground.. The time taken by the animal to recover is recorded with a maximum time of 2 min. On days 3, 5, 7 and 9, a cliff drop aversion test is made between 14:00 and 18:00 h, and on days 2, 4, 6 and 8, a quantification of ultrasounds is made, also between 14:00 and 18:00 h. In the cliff drop aversion test, the pup is placed on the edge of a platform Žwhich is 16 cm high. with its forepaws and face over the edge. The animal will turn and crawl away from the cliff drop. The turn-away time is noted, as well as any fall off the platform. The emission of ultrasounds is obtained by suspending the pup by the tail 40 s. The ultrasounds are conveyed into audible signals by an S25 Bat Detector, so that the experimentator can note the number of ultrasounds emitted. In the study, 274 pups were tested and 28 were mutants. For practical reasons, the composition and the size of the groups differed at each age. On the entire period studied, the number of mutants composing a group Žnoted NŽsg.. varied from 8 to 27 and the number of non-mutants ŽNŽn.. from 24 to 56. Consequently, no longitudinal study was possible and data concerning staggerers and non-staggerers were compared age by age, using the t-test for quantitative data and using x 2 or the Fisher exact probability test Ždepending on the size of the groups. for qualitative data. 3. Results
Fig. 2. Righting test: mean time to regain normal position and standard error. ) ) P - 0.03, ) ) ) P - 0.01.
ŽNŽsg. s 16, NŽn. s 35, t s y2.1, P - 0.05., day 4 ŽNŽsg. s 17, NŽn. s 36, t s y2.6, P - 0.03., day 6 ŽNŽsg. s 18, NŽn. s 41, t s y2.1, P - 0.05. and day 8 ŽNŽsg. s 20, NŽn. s 54, t s y2.6, P - 0.03.. 3.2. Righting test In both groups, some animals did not succeed in righting themselves in 2 min until day 6, but there are no significant differences Žat day 2, 2% of non-mutants did not succeed in 2 min versus 40% in mutants; at day 3, 2% of non-mutants failed versus 25%; at day 4, 12% of non-mutants failed versus 33%; at day 5, 3% of nonmutants failed versus 1% and at day 6, 4% of non-mutants failed versus 2%.. Considering those that did succeed in 2 min, the mutants are usually less efficient than non-mutants; they take more time to right themselves, especially on day 3 ŽNŽsg. s 15, NŽn. s 32, t s 2.9, P - 0.01., day 7 ŽNŽsg. s 19, NŽn. s 56, t s 2.3, P - 0.03., day 8 ŽNŽsg. s 27, NŽn. s 54, t s 2.6, P - 0.03. and day 9 ŽNŽsg. s 22, NŽn. s 50, t s 3.1, P - 0.01. ŽFig. 2.. 3.3. Cliff drop aÕersion test There is no difference between the two groups in terms of time taken to turn away from the cliff. But, as shown in
3.1. Weight The mutant’s weight is lower during the entire period studied ŽFig. 1., with significant differences on day 3
Fig. 1. Evolution of weight from 2 to 9 days, mean values and standard error, ) P - 0.05, ) ) P - 0.03.
Fig. 3. Cliff drop aversion test: proportion of animals falling off the cliff. The fractions indicate how many of all animals tested fell. ) ) P - 0.03, ))) P - 0.01. At day 3, x 2 s 7.76, P s 0.005, day 5, Fisher’s test, P s 0.08, day 7, x 2 s6.75, P s 0.009, day 9, Fisher’s test, P s 0.06.
P. Heuze´ et al.r DeÕelopmental Brain Research 101 (1997) 81–84
Fig. 4. Number of ultrasonic vocalisations, mean values and standard error, ) ) P - 0.03.
Fig. 3, the proportion of animals falling off the cliff is more important in the staggerer group. 3.4. Ultrasounds Staggerers emit more ultrasounds than normal mice at 6 days ŽNŽsg. s 9, NŽn. s 19, t s 2.6, P - 0.03. and 8 days ŽNŽsg. s 16, NŽn. s 38, t s 2.4, P - 0.03.. In fact, the number of ultrasounds in normal mice decreases between day 4 and 6, with staggerers, it decreases between day 6 and 8 ŽFig. 4..
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staggerers, thermoregulation processes could be initiated a couple of days later, and as a result, they emit more ultrasounds than normal mice when isolated from the nest – i.e. source of heat – at 6 and 8 days. In conclusion, our study shows the existence of behavioral and physical Ži.e. weight. deficiencies in staggerer as early as the third day of age. Furthermore, from 6 to 9 days of age, it is clear that the staggerers differ from the non-mutants in weight, time taken to right themselves, capacity to avoid falling from the cliff and quantity of ultrasounds emitted. In the adult staggerer, both weight loss and motor deficiency are maintained. But it is possible to improve staggerer motor performance by placing the animal in a special set-up that stimulates its vestibular system w6x. Some of the socially abnormal behavior described in the Introduction can also be partly overcome. For example, a male staggerer may exhibit sexual behavior toward a receptive female when reared from the age of 40 days with several normal females w5x. In other words, particular post-weaning social environments can provoke behavior that is absent because of mutation. The environment being an active factor of the behavioral development of the staggerer mutant, it would be interesting to investigate the influence of pre-weaning special environments on staggerers identified few days after birth.
Acknowledgements 4. Discussion The aim of this study was to distinguish mutants from non-mutants before the age of 9 days, by using behavioral and physical tests. Differences were found as early as the third day of life in all the motor tests used. Staggerers weighed less during the entire period. This mutant characteristic is maintained as the animal grows up; the difference of weight has already been shown in juvenile staggerer of 40 days old w4x. During the righting tests, there was a significant difference in performance at day three but not the day immediately following. Pups from 1 to 4 days did not appear to coordinate their movements correctly in righting themselves w1x and there was an important interindividual variation in the time taken to regain normal position. On the other hand, on days 7, 8 and 9, it was clear that non-mutants always succeeded easily in righting themselves. The mutants also succeeded, but not as quickly and easily. In the cliff drop aversion tests, all animals attempted to recoil in order to avoid falling but the staggerers were less efficient and the proportion of pups that fell over the cliff was greater in mutants. Regarding ultrasound production, it is well known that the number of calls with normal mice increases until 4 or 5 days of age, then decreases until about 15 days of age and the lowering of the calls at 5 days is correlated with the beginning of homeothermal development w10,11x. In
We thank Simone Demouron for taking care of the mutants, Bob Flyn for his help in writing the manuscript and Gerard Martin for his comments and technical support. ´
References w1x J. Altman, K. Sudarshan, Postnatal development of locomotion in the laboratory rat, Anim. Behav. 23 Ž1975. 893–920. w2x C. Baudoin, C. Feron, V. Deiss, Olfactory deficit induced by the ´ murine staggerer mutation: behavioural data, in: R. Apfelbach, D. Muller-Schwarze, K. Reutter, E. Weiler ŽEds.., Chemical Signals in ¨ Vertebrates VII, Advances in the Biosciences, vol. 93, Pergamon Elsevier, 1994, 413–419. w3x S. Boufares, J.M. Guastavino, K. Larsson, Restoration of staggerer mouse maternal behavior following long term breeding selection, Physiol. Behav. 53 Ž1993. 1151–1155. w4x C. Feron, Les comportements socio-sexuels des souris staggerer ´ males: caracteristiques et effets de l’experience sociale. These ˆ ´ ´ ` d’Universite. ´ Universite´ Paris XIII, 1992, 181 pp. w5x C. Feron, C. Baudoin, M.S. Magnusson, Effect of post-weaning ´ social experience with normal female on the behaviour of adult male staggerer mice interacting with normal females, Behav. Process. 23 Ž1991. 142–152. w6x G. Goodall, J.M. Guastavino, C. Feron, Adaptation and behavioural ´ plasticity: an investigation of a neurological mutant mouse, in: V. Leonovicovd, V.J.A. Novak ŽEds.., Behaviour as One of the Main Factor of Evolution, Czechoslovak Academy Sciences Praha, 1987, 173–192.
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P. Heuze´ et al.r DeÕelopmental Brain Research 101 (1997) 81–84
w7x K. Herrup, Role of staggerer gene in determining cell number in cerebellar cortex I. Granule cell death is an indirect consequence of staggerer gene action, Dev. Brain Res. 11 Ž1983. 267–274. w8x D.M.D. Landis, R.L. Sidman, Electron microscopic analysis of postnatal histogenesis in the cerebellar cortex of staggerer mutant mice, J. Comp. Neurol. 179 Ž1978. 831–864. w9x R. Misslin, M. Cigrang, J.M. Guastavino, Responses to novelty in staggerer mutant mice, Behav. Process. 12 Ž1986. 51–56. w10x E. Noirot, D. Pye, Sound analysis of ultrasonic distress calls of mouse pups as a function of their age, Anim. Behav. 17 Ž1969. 340–349.
w11x E. Okon, Factors affecting ultrasound production in infant rodents, J. Zool. London 168 Ž1972. 139–148. w12x H. Zanjani, N. Delhaye-Bouchaud, J. Mariani, Decreased number of cells in the inferior olivary nucleus of the developing staggerer mouse, Dev. Brain Res. 21 Ž1985. 141–146. w13x H. Zanjani, N. Delhaye-Bouchaud, J. Mariani, K. Herrup, Neuronal cell loss in heterozygous staggerer mutant mice: a model for genetic contributions to the aging process, Dev. Brain Res. 67 Ž1991. 153–160.