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

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.