Neuroanatomic and behavioral traits for autistic disorders in age-specific restricted index selection mice

L. Meng, Lu Lu, K. M. Murphy, C. M. Yuede, J. M. Cheverud, J. G. Csernansky, H. Dong

Research output: Contribution to journalArticle

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Abstract

The pathogenesis of neurodevelopmental disorders such as autism is believed to be influenced by interactions between genetic and environmental factors, and appropriate animal models are needed to assess the influence of such factors on relevant neurodevelopmental phenotypes. A set of inbred mouse strains (Atchley strains) including A12 (E+L0) and A22 (E-L0) were generated by age-specific restricted index selection from a baseline random-bred ICR mouse population obtained from Harlan Sprague-Dawley [Atchley et al. (1997) Genetics 146(2):629-640; Indianapolis, IN, USA). As compared with the A22 strain, A12 mice had significantly increased early (P0-P10) body weight gain with minimal changes in late (P28-P56) body weight gain. We found that these strains also differed in brain weight, brain volume, cell proliferation, and FGF-2 levels in certain brain regions. Specifically, brain weight and volume were significantly greater in A12 mice than that in A22 mice at P10 and P28. Quantitative analysis of bromodeoxyuridine (BrdU) labeling of proliferating cells showed that the number of BrdU-positive cells in the A12 strain were significantly greater in the frontal cortex and lesser in the dentate gyrus than that in the A22 strain at P28. Western blot revealed that fibroblast growth factors-2 (FGF-2), but not brain-derived neurotrophic factor (BDNF), expression was significantly increased in the frontal cortex of A12 strain at P28. Also, A12 mice exhibited decreased intra-strain social interaction and increased repetitive stereotyped behaviors at P28. Our study suggests that A12 mice may partially mimic the anatomic and behavioral traits of patients with neurodevelopmental disorders such as autism spectrum disorders, and therefore may yield insights into the developmental mechanisms involved in their pathogenesis.

Original languageEnglish (US)
Pages (from-to)215-222
Number of pages8
JournalNeuroscience
Volume189
DOIs
StatePublished - Aug 25 2011
Externally publishedYes

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compound A 12
Autistic Disorder
Brain
Frontal Lobe
Fibroblast Growth Factor 2
Bromodeoxyuridine
Weight Gain
Body Weight
Stereotyped Behavior
Weights and Measures
Inbred ICR Mouse
Inbred Strains Mice
Brain-Derived Neurotrophic Factor
Dentate Gyrus
Interpersonal Relations
Animal Models
Cell Count
Western Blotting
Cell Proliferation
Phenotype

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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Neuroanatomic and behavioral traits for autistic disorders in age-specific restricted index selection mice. / Meng, L.; Lu, Lu; Murphy, K. M.; Yuede, C. M.; Cheverud, J. M.; Csernansky, J. G.; Dong, H.

In: Neuroscience, Vol. 189, 25.08.2011, p. 215-222.

Research output: Contribution to journalArticle

Meng, L. ; Lu, Lu ; Murphy, K. M. ; Yuede, C. M. ; Cheverud, J. M. ; Csernansky, J. G. ; Dong, H. / Neuroanatomic and behavioral traits for autistic disorders in age-specific restricted index selection mice. In: Neuroscience. 2011 ; Vol. 189. pp. 215-222.
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