Survey of 21 inbred mouse strains in two laboratories reveals that BTBR T/+ tf/tf has severely reduced hippocampal commissure and absent corpus callosum

Wahłsten, Douglas; Metten, Pamela; Crabbe, John C.

doi:10.1016/s0006-8993(03)02354-0

Cited by 188 publications

(175 citation statements)

References 24 publications

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“…DTI is a technique that examines the underlying tissue microstructure based on the diffusion of water throughout the brain. The most striking difference between BTBR and both of the control strains was the almost complete lack of a corpus callosum, as previously reported [150]. Cerebral white matter as a whole was significantly reduced, specifically 10 of 14 with matter regions were smaller.…”

Section: Recent Investigations (2010-14)supporting

confidence: 77%

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

2015

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In order to understand the consequences of the mutation on behavioral and biological phenotypes relevant to autism, mutations in many of the risk genes for autism spectrum disorder have been experimentally generated in mice. Here, we summarize behavioral outcomes and neuroanatomical abnormalities, with a focus on highresolution magnetic resonance imaging of postmortem mouse brains. Results are described from multiple mouse models of autism spectrum disorder and comorbid syndromes, including the 15q11-13, 16p11.2, 22q11.2, Cntnap2, Engrailed2, Fragile X, Integrinβ3, MET, Neurexin1a, Neuroligin3, Reelin, Rett, Shank3, Slc6a4, tuberous sclerosis, and Williams syndrome models, and inbred strains with strong autism-relevant behavioral phenotypes, including BTBR and BALB. Concomitant behavioral and neuroanatomical abnormalities can strengthen the interpretation of results from a mouse model, and may elevate the usefulness of the model system for therapeutic discovery.

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Section: Recent Investigations (2010-14)supporting

confidence: 77%

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

2015

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“…ANOVAs comparing all possible pairs of data sets and details of methods for measuring brains in each study are provided in Tables 1 and 2 and Supporting Text, which are published as supporting information on the PNAS web site. The Edmonton and Portland strain means were very similar indeed (r ϭ 0.98), and average weights across all strains were almost identical at the two sites (0.452 and 0.456 g, respectively) (15). Methods of fixation were very similar in the Williams (16) study, and the correlation of Edmonton data with their strain means was very high (r ϭ 0.88).…”

mentioning

confidence: 73%

Stability of inbred mouse strain differences in behavior and brain size between laboratories and across decades

Wahłsten

Bachmanov

Finn

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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If we conduct the same experiment in two laboratories or repeat a classical study many years later, will we obtain the same results? Recent research with mice in neural and behavioral genetics yielded different results in different laboratories for certain phenotypes, and these findings suggested to some researchers that behavior may be too unstable for fine-scale genetic analysis. Here we expand the range of data on this question to additional laboratories and phenotypes, and, for the first time in this field, we formally compare recent data with experiments conducted 30 -50 years ago. For ethanol preference and locomotor activity, strain differences have been highly stable over a period of 40 -50 years, and most strain correlations are in the range of r ‫؍‬ 0.85-0.98, as high as or higher than for brain weight. For anxiety-related behavior on the elevated plus maze, on the other hand, strain means often differ dramatically across laboratories or even when the same laboratory is moved to another site within a university. When a wide range of phenotypes is considered, no inbred strain appears to be exceptionally stable or labile across laboratories in any general sense, and there is no tendency to observe higher correlations among studies done more recently. Phenotypic drift over decades for most of the behaviors examined appears to be minimal.agonistic behavior ͉ anxiety ͉ ethanol preference ͉ gene-environment interaction ͉ locomotor activity

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“…BTBR mice do not demonstrate significant quadrant selectivity after reversal learning in the Morris water maze task, which may indicate a resistance to change in this strain [49]. It is possible that the behavioral phenotype of low social approach [8,49] and failure to modify behavioral patterns in the hole-board familiarization assay might be related to the overt neuroanatomical defects in these mice, including absent corpus callosum and reductions in the hippocampal commissure [82]. Some studies have reported deficiencies in corpus callosum volume or white matter concentration in autistic patients [1,13,41,61,81,83].…”

Section: Discussionmentioning

confidence: 99%

“…82 Figure 12 depicts the results from the olfactory stimuli tests, before and after familiarization, in the wildtype and NMDA receptor-deficient mice. Before familiarization, the wildtype mice evidenced an extreme preference for the familiar cage bedding, with almost 40% of the total responses across the 16 holes directed toward this olfactory stimulus.…”

Section: Studymentioning

confidence: 99%

Development of a mouse test for repetitive, restricted behaviors: Relevance to autism

Moy

Nadler

Poe

et al. 2008

Behavioural Brain Research

178

182

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Repetitive behavior, a core symptom of autism, encompasses stereotyped responses, restricted interests, and resistance to change. These studies investigated whether different components of the repetitive behavior domain could be modeled in the exploratory hole-board task in mice. Four inbred mouse strains, C57BL/6J, BALB/cByJ, BTBR T + tf/J, and FVB/NJ, and mice with reduced expression of Grin1, leading to NMDA receptor hypofunction (NR1 neo/neo mice), were tested for exploration and preference for olfactory stimuli in an activity chamber with a 16-hole floor-board. Reduced exploration and high preference for holes located in the corners of the chamber were observed in BALB/cByJ and BTBR T+tf/J mice. All inbred strains had initial high preference for a familiar olfactory stimulus (clean cage bedding). BTBR T + tf/J was the only strain that did not demonstrate a shift in hole preference towards an appetitive olfactory stimulus (cereal or a chocolate chip), following home cage exposure to the food. The NR1 neo/neo mice showed lower hole selectivity and aberrant olfactory stimulus preference, in comparison to wildtype controls. The results indicate that NR1 neo/neo mice have repetitive nose poke responses that are less modified by environmental contingencies than responses in wildtype mice. 25-30% of NMDA-receptor hypomorphic mice also show self-injurious responses. Findings from the olfactory studies suggest that resistance to change and restricted interests might be modeled in mice by a failure to alter patterns of hole preference following familiarization with an appetitive stimulus, and by high preference persistently Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

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Survey of 21 inbred mouse strains in two laboratories reveals that BTBR T/+ tf/tf has severely reduced hippocampal commissure and absent corpus callosum

Cited by 188 publications

References 24 publications

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

Stability of inbred mouse strain differences in behavior and brain size between laboratories and across decades

Development of a mouse test for repetitive, restricted behaviors: Relevance to autism

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