Cognitive deficits in Tsc1+/−mice in the absence of cerebral lesions and seizures

Tuberous sclerosis complex (TSC) is characterized by brain lesions, epilepsy, increased incidence of mental retardation and autism. The causal link between lesion load and epilepsy on cognitive disabilities has been debated, and these factors explain only part of the intelligence quotient variability. A Tsc2 rat model of the disease provided evidence that the TSC genes are directly involved in neuronal function. However, these lesion‐ and epilepsy‐free animals did not show learning deficits, leaving open the possibility that the presence of brain lesions or epilepsy is a prerequisite for the cognitive deficits to fully develop. Here, we reinvestigated the relation among cerebral lesions, epilepsy, and cognitive function using Tsc1+/−mice.

[1]  Christopher J Howe,et al.  The tuberous sclerosis complex proteins--a GRIPP on cognition and neurodevelopment. , 2007, Trends in molecular medicine.

[2]  F. Jensen,et al.  A Mouse Model of Tuberous Sclerosis: Neuronal Loss of Tsc1 Causes Dysplastic and Ectopic Neurons, Reduced Myelination, Seizure Activity, and Limited Survival , 2007, The Journal of Neuroscience.

[3]  G. Holmes,et al.  Tuberous Sclerosis Complex and Epilepsy: Recent Developments and Future Challenges , 2007, Epilepsia.

[4]  E T Bullmore,et al.  Neuroanatomical correlates of memory deficits in tuberous sclerosis complex. , 2007, Cerebral cortex.

[5]  D. Lipsker,et al.  Tuberous Sclerosis Complex. , 2021, Urology.

[6]  M. Sheng,et al.  The growing role of mTOR in neuronal development and plasticity , 2006, Molecular Neurobiology.

[7]  V. Wong.  Study of the Relationship Between Tuberous Sclerosis Complex and Autistic Disorder , 2006, Journal of child neurology.

[8]  P. Khong,et al.  Tuberous Sclerosis Complex: Correlation of Magnetic Resonance Imaging (MRI) Findings With Comorbidities , 2006, Journal of child neurology.

[9]  H. Beck,et al.  Impaired synaptic plasticity in a rat model of tuberous sclerosis , 2006, The European journal of neuroscience.

[10]  J. Dichgans,et al.  Enhanced episodic‐like memory and kindling epilepsy in a rat model of tuberous sclerosis , 2006, Journal of neurochemistry.

[11]  Bernardo L Sabatini,et al.  Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2 , 2005, Nature Neuroscience.

[12]  D. Griffiths,et al.  A mouse model of tuberous sclerosis 1 showing background specific early post-natal mortality and metastatic renal cell carcinoma. , 2005, Human molecular genetics.

[13]  Alain Verloes,et al.  Specific Genetic Disorders and Autism: Clinical Contribution Towards their Identification , 2005, Journal of autism and developmental disorders.

[14]  P. Bolton,et al.  Standardized Whole Brain Mapping of Tubers and Subependymal Nodules in Tuberous Sclerosis Complex , 2004, Journal of child neurology.

[15]  P. Schwartzkroin,et al.  Morphology of cerebral lesions in the Eker rat model of tuberous sclerosis , 2004, Acta Neuropathologica.

[16]  T. Harris,et al.  The relation of infantile spasms, tubers, and intelligence in tuberous sclerosis complex , 2004, Archives of Disease in Childhood.

[17]  L. Cantley,et al.  Rheb fills a GAP between TSC and TOR. , 2003, Trends in biochemical sciences.

[18]  P. Bolton,et al.  Learning disability and epilepsy in an epidemiological sample of individuals with tuberous sclerosis complex , 2003, Psychological Medicine.

[19]  Hongbing Zhang,et al.  Tsc2 Null Murine Neuroepithelial Cells Are a Model for Human Tuber Giant Cells, and Show Activation of an mTOR Pathway , 2002, Molecular and Cellular Neuroscience.

[20]  Hongbing Zhang,et al.  A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells. , 2002, Human molecular genetics.

[21]  E. T. Bullmore,et al.  Widespread anatomical abnormalities of grey and white matter structure in tuberous sclerosis , 2001, NeuroImage.

[22]  H. Vinters,et al.  The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho , 2000, Nature Cell Biology.

[23]  H. Onda,et al.  Tsc2(+/-) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background. , 1999, The Journal of clinical investigation.

[24]  T. Noda,et al.  Renal carcinogenesis, hepatic hemangiomatosis, and embryonic lethality caused by a germ-line Tsc2 mutation in mice. , 1999, Cancer research.

[25]  K. Artzt,et al.  Loss of function of the tuberous sclerosis 2 tumor suppressor gene results in embryonic lethality characterized by disrupted neuroepithelial growth and development. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[26]  A. Knudson,et al.  Predisposition to renal carcinoma in the Eker rat is determined by germ-line mutation of the tuberous sclerosis 2 (TSC2) gene. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[27]  C. Shepherd,et al.  A prevalence study of autism in tuberous sclerosis , 1993, Journal of autism and developmental disorders.

[28]  Joseph E LeDoux,et al.  Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. , 1992, Behavioral neuroscience.

[29]  R. Morris,et al.  Place navigation impaired in rats with hippocampal lesions , 1982, Nature.

[30]  Y. Kubo,et al.  A germline insertion in the tuberous sclerosis (Tsc2) gene gives rise to the Eker rat model of dominantly inherited cancer , 1995, Nature Genetics.