Mecp2 deficiency is associated with learning and cognitive deficits and altered gene activity in the hippocampal region of mice.
Rett syndrome (RTT) is a debilitating neurological condition associated with mutations in the X-linked MECP2 gene, where apparently normal development is seen prior to the onset of cognitive and motor deterioration at 6-18 months of life. A targeted deletion of the methyl-CpG-binding domain (MBD) coding region and disruption of mRNA splicing was introduced in the mouse, resulting in a complete loss of Mecp2 transcripts and protein. Postnatal comparison of XO and XY mutant Mecp2 allele-containing null mice revealed similar effects on mouse growth and viability, suggesting that phenotypic manifestations are not modulated by the Y-chromosome. Further assessment of Mecp2-null XY mice highlighted cerebellar and hippocampal/amygdala-based learning deficits in addition to reduced motor dexterity and decreased anxiety levels. Brain tissues containing the hippocampal formation of XY Mecp2-null mice also displayed significant changes in genetic activity, which are related to the severity of the mutant phenotype.
Embryology Unit, Children's Medical Research Institute,Wentworthville, NSW, Australia.
Gregory J
GJ
Pelka
Catherine M
CM
Watson
Tania
T
Radziewic
Melinda
M
Hayward
Hooshang
H
Lahooti
John
J
Christodoulou
Patrick P L
PP
Tam
D000818:Animals; D001007:Anxiety; D003214:Conditioning, Classical; D018450:Disease Progression; D005239:Fear; D005786:Gene Expression Regulation; D018390:Gene Targeting / Q000379:methods; D006624:Hippocampus / Q000378:metabolism*; D007858:Learning; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009043:Motor Activity; D010641:Phenotype; D015518:Rett Syndrome / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D014998:Y Chromosome / Q000502:physiology
D051783:Methyl-CpG-Binding Protein 2