Genetic variation in paw preference (handedness) in the mouse

Biddle, Fred G.; Coffaro, Cristina M.; Ziehr, Jeanette E.; Eales, Brenda A.

doi:10.1139/g93-123

Cited by 53 publications

(49 citation statements)

References 18 publications

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“…This decrease in lateralization was observed for the three DAT strains that are normally contrasted for their degree of paw preference. Indeed, WT mice of the B6-DAT strain were found to be more strongly lateralized than the D2-DAT, as previously described for the B6 and D2 inbred strains of mice (Biddle et al, 1993;Signore et al, 1991a). In addition, the DAT-F 1 hybrid strain was similar to its highly lateralized B6 parental strain, supporting a dominant model for the higher degree of lateralization.…”

Section: Discussionsupporting

confidence: 81%

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Constitutive Hyperdopaminergia is Functionally Associated with Reduced Behavioral Lateralization

Morice

Denis

Macario

et al. 2004

Neuropsychopharmacol

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According to the dopamine (DA) hypothesis of schizophrenia and the strong evidence for decreased cerebral lateralization in schizophrenic patients, we postulated that hyperactivity of the dopaminergic system could be associated with a reduced behavioral lateralization in mice. Mice lacking the dopamine transporter (DAT) gene were used as a genetic model of persistent hyperdopaminergia. The DAT null mutation was transferred on C57BL/6JOrl (B6) and DBA/2JOrl (D2) inbred backgrounds for more than 10 generations of backcrossing to derive three DAT strains, B6, D2, and B6 Â D2(F 1 ). Adult mutant mice of the three DAT strains and their littermates were tested for paw preference using Collins' protocol. Our results demonstrated that, whatever the genetic background, persistent hyperdopaminergia directly impairs the degree of lateralization without affecting the direction. Our results support the degree of lateralization as a good candidate phenotype to further improve genetic analysis of cerebral lateralization in normal and pathological conditions. Neuropsychopharmacology Keywords: schizophrenia; direction and degree of asymmetry; paw preference; knockout mice; cocaine INTRODUCTIONAnomalies in behavioral, neuroanatomical, and neurophysiological asymmetry have been widely documented in schizophrenic patients, supporting lateralization as a good candidate symptom that could contribute to clarifying schizophrenia heterogeneity (Leboyer et al, 1998). A metaanalysis of 19 studies on schizophrenia showed that the prevalence of non-right-handedness was significantly higher in patients than in healthy subjects (Sommer et al, 2001). Similarly, in the meta-analysis of three prospective followup studies, pre-schizophrenic subjects were significantly more often non-right-handed than the general population (Sommer et al, 2001). Furthermore, in vivo imaging studies of schizophrenia have provided evidence that the right-left asymmetry of the dopamine (DA) synthesis capacity and of the dopamine transporter (DAT) binding in the caudate are both lost in antipsychotic-naive patients (Hietala et al, 1999(Hietala et al, , 1995Hsiao et al, 2003;Laakso et al, 2000). In addition, neuroleptics are able to change the balance of hemispheric activity, thus improving left-hemispheric attentional processes (for a review, see Gruzelier, 1999), and a recent study demonstrated that haloperidol-induced downregulation of DA synthesis was significantly greater in the left than in the right striatum (Grunder et al, 2003). Finally, a highly significant correlation was reported between depressive symptoms in antipsychotic-naive schizophrenia and DA synthesis capacity in the left striatum (Hietala et al, 1999).Taken together, these data support the hypothesis of a potential link between cerebral lateralization and schizophrenia, and suggest that abnormal asymmetry of the dopaminergic transmission could be one of the key neurobiological substrates for this functional relationship. Based on the DA hypothesis of schizophrenia, which attributes the positive sc...

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Section: Discussionsupporting

confidence: 81%

“…These progenitor strains were chosen because they are among the most genetically, physiologically, and behaviorally contrasted inbred strains (Atchley and Fitch, 1991; PuglisiAllegra and Cabib, 1997). In terms of handedness, B6 have been described as strongly lateralized, whereas D2 were found to be ambidextrous (Biddle et al, 1993;Signore et al, 1991a). …”

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confidence: 99%

Constitutive Hyperdopaminergia is Functionally Associated with Reduced Behavioral Lateralization

Morice

Denis

Macario

et al. 2004

Neuropsychopharmacol

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“…Thus, although Lmo4 expression in mouse cortex was moderately asymmetrical in every individual brain tested so far, it was not consistently lateralized to the right or left side. This may relate to behavioral and anatomical studies in mice, in which sensory-motor asymmetries, like paw preference, are observed in individual mice, but are not biased on a population level to either the right or left hemisphere as is hand preference in humans (10)(11)(12)(13)(14). The differences in mice and humans suggest the intriguing possibility that paw preference in rodents might reflect an early, perhaps stochastic, developmental asymmetry that is established perinatally, prior to paw usage, implying a transcriptional asymmetry that is not consistently lateralized to the left and right.…”

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confidence: 98%

Early Asymmetry of Gene Transcription in Embryonic Human Left and Right Cerebral Cortex

Sun

Patoine

Abu-Khalil

et al. 2005

Science

334

271

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The human left and right cerebral hemispheres are anatomically and functionally asymmetric. To test whether human cortical asymmetry has a molecular basis, we studied gene expression levels between the left and right embryonic hemispheres using Serial Analysis of Gene Expression (SAGE), and identified and verified 27 differentially expressed genes, suggesting that human cortical asymmetry is accompanied by early, striking transcriptional asymmetries. LMO4 is consistently more highly expressed in the right perisylvian human cerebral cortex than in the left, and is essential for cortical development in mice, suggesting that human left-right specialization reflects asymmetric cortical development at early stages.One of the most remarkable aspects of the human cerebral cortex is that the two hemispheres are specialized for distinct cognitive and behavioral functions. Whereas the right cerebral cortex regulates movement of the left side of the body and vice versa, approximately 90% of the human population is naturally more skilled with the right hand than with the left (1). This motor asymmetry is strongly correlated with language dominance: language function is predominantly localized to a distributed network in the left perisylvian cortex in 97% of righthanders and about 60% of left-handers (2,3). Functional asymmetries exist in mathematical ability, and spatial and facial recognition as well. These functional asymmetries have been related to anatomical asymmetries of the cortex that are somewhat more subtle (2,4). For example, the posterior end of the Sylvian fissure, is higher in the right hemisphere than in the left (5). The planum temporale, a region in the posterior portion of the superior temporal sulcus in which Wernike's area resides, is larger in the left than in the right in more than 65% of examined adult and 56-79% of fetuses or infant brains, so that the anatomical asymmetries are less striking than the functional ones (6,7). Although genetic factors connecting cerebral Here we directly tested the hypothesis that left-right cortical asymmetry in humans results from differential gene expression at early embryonic stages, long before the onset of organized cerebral cortical function. By applying Serial Analysis of Gene Expression (SAGE), we measured gene expression levels between the left and right hemispheres in early (12-14 weeks) embryonic human brains, during periods of neuronal proliferation and migration, and later (19 weeks), after these processes are largely completed (9). Brain tissues were first dissected from matching perisylvian regions in two hemispheres (Fig. 1, A to C). The cortex was then separated at the midline. On the medial side of the hemisphere, tissues were also dissected from the ventricular zone in the frontal and occipital regions (Fig. 1B). Total RNA was isolated and 14 SAGE libraries were generated (Fig. 1D). To detect genes with differential expression levels, we compared tag frequency for each gene between two SAGE libraries generated from the frontal, perisylvian an...

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“…Be that as it may, as Collins himself has pointed out, the usefulness of the mouse handedness model is not predicated on the similarity of its distribution of handedness types to those of other species [8]. Biddle's group [13] has also recently reported strain differences in RPE scores and our own independent reanalysis of the Signore et al data supports both a leftward population bias and strain differences in RPE 2 . The Collins test has been a very popular method for determining paw preference in mice; several groups of workers have employed this procedure to investigate the influences of various factors on mouse paw preference [14][15][16][17][18][19]11].…”

Section: Introductionmentioning

confidence: 53%

Mouse paw preference: effects of variations in testing protocol

Bulman-Fleming

Bryden

Rogers

1997

Behavioural Brain Research

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Two experiments using two inbred strains of mice were conducted to study mouse paw preference. In the first study, 250 (50× 5) paw reaches from each of 12 male and 12 female C57BL/6J mice were observed over an 8-week period using the Collins paw preference apparatus to investigate questions relating to the independence of reaches, the size of the tube into which the animals reach for flakes of food, and practise effects. Animals appeared to be much more highly lateralized when two independent reaches per day for 25 days (I protocol) were observed than when 50 reaches were observed in a single session (S protocol). Paradoxically, however, we found no evidence for the lack of independence of reaches when we examined the sequences of reaches performed by animals under the S protocol conditions. With practise, animals became slightly more lateralized, but there were no effects of sex, and approximately equal numbers of mice were left-pawed as were right-pawed. The size of the tube had no effect. The second study used 30 BALB mice, each of which was tested with both the I and S protocols, with order of testing counterbalanced. There was a significant protocol×order interaction such that those doing S first were more highly lateralized on the I task, but those doing I first were highly lateralized on both tasks. © 1997 Elsevier Science Ireland B.V.

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Genetic variation in paw preference (handedness) in the mouse

Cited by 53 publications

References 18 publications

Constitutive Hyperdopaminergia is Functionally Associated with Reduced Behavioral Lateralization

Constitutive Hyperdopaminergia is Functionally Associated with Reduced Behavioral Lateralization

Early Asymmetry of Gene Transcription in Embryonic Human Left and Right Cerebral Cortex

Mouse paw preference: effects of variations in testing protocol

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