title: Heterozygosity for the mutated X-chromosome-linked L1 cell adhesion molecule gene leads to increased numbers of neurons and enhanced metabolism in the forebrain of female carrier mice.
abstract: Mutations in the X-chromosomal L1CAM gene lead to severe neurological deficits. In this study, we analyzed brains of female mice heterozygous for L1 (L1+/-) to gain insights into the brain structure of human females carrying one mutated L1 allele. From postnatal day 7 onward into adulthood, L1+/- female mice show an increased density of neurons in the neocortex and basal ganglia in comparison to wild-type (L1+/+) mice, correlating with enhanced metabolic parameters as measured in vivo. The densities of astrocytes and parvalbumin immunoreactive interneurons were not altered. No significant differences between L1+/- and L1+/+ mice were seen for cell proliferation in the cortex during embryonic days 11.5-15.5. Neuronal differentiation as estimated by analysis of doublecortin-immunoreactive cortical cells of embryonic brains was similar in L1+/- and L1+/+ mice. Interestingly, at postnatal days 3 and 5, apoptosis was reduced in L1+/- compared to L1+/+ mice. We suggest that reduced apoptosis leads to increased neuronal density in adult L1+/- mice. In conclusion, L1+/- mice display an unexpected phenotype that is not an intermediate between L1+/+ mice and mice deficient in L1 (L1-/y), but a novel phenotype which is challenging to understand regarding its underlying molecular and cellular mechanisms.
authors.affiliation: Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
authors.forename: Janinne Sylvie
authors.initials: JS
authors.lastname: Schmid
authors.forename: Christian
authors.initials: C
authors.lastname: Bernreuther
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Nikonenko
authors.forename: Zhang
authors.initials: Z
authors.lastname: Ling
authors.forename: Günter
authors.initials: G
authors.lastname: Mies
authors.forename: Konstantin-A
authors.initials: KA
authors.lastname: Hossmann
authors.forename: Igor
authors.initials: I
authors.lastname: Jakovcevski
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001345:Autoradiography; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D005260:Female; D050172:Genes, X-Linked / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007395:Interneurons / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics*; D010641:Phenotype; D016548:Prosencephalon / Q000166:cytology* / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D039842:Neural Cell Adhesion Molecule L1; D001973:Bromodeoxyuridine