Elsevier

Gene Expression Patterns

Volume 9, Issue 6, September 2009, Pages 423-429
Gene Expression Patterns

Spatiotemporal expression in mouse brain of Kiaa2022, a gene disrupted in two patients with severe mental retardation

https://doi.org/10.1016/j.gep.2009.06.001Get rights and content

Abstract

We previously identified an inactivating disruption of the X-linked KIAA2022 gene by a chromosomal rearrangement in two male patients with severe mental retardation. In order to determine if KIAA2022 has a role during the development of the central nervous system, we have cloned its murine ortholog, Kiaa2022, determined its genomic structure and studied its expression during mouse development. We show that Kiaa2022 is preferentially expressed in the central nervous system and that the transcript is highly expressed in postmitotic neurons. The expression of Kiaa2022 is first detectable at E10.5 to reach a maximum at P3 where it is notably expressed in the hippocampus, the entorhinal cortex and strongly in the ventral premammillary nucleus. After P3, the expression of Kiaa2022 decreases and maintains very low levels thereafter. Our results show that Kiaa2022 is expressed in the developing brain and that it may play a role in postmitotic, maturing neurons.

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Results and discussion

The mammalian X chromosome is enriched with genes expressed in the brain, as demonstrated by the high incidence of X-linked neurological disorders (Skuse, 2005, Nguyen and Disteche, 2006).

We have previously described two living related male adolescents harboring the same disruption of the KIAA2022 gene on the X chromosome (Cantagrel et al., 2004). Both patients display a similar, although complex, phenotype. The older patient was presenting febrile seizures and oculogyric crisis in infancy. A

Animals

Pregnant mice (C57BL/6) were obtained from the Janvier breeding center (Elevage Janvier, Le Genest Saint Isle, France). Temporal profile of Kiaa2022 expression during the development was initially assessed using real time quantitative PCR using mRNAs extracted from either whole embryo at E10.5, E12.5, E15.5 and E18.5 or whole brain at P0 (birth), P3, P10 and P45. Localization of Kiaa2022 expression during the development was studied by in situ hybridization at E11.5, E12.5, E13.5, P3 and P45.

Acknowledgements

We thank Pierre-Yves Risold for helpful discussions and Vincent Nieoullon for technical advice. We thank Jean-Charles Viemari for advice concerning the preparation and labeling of medulla samples. VC is a recipient of a grant from the Ministère de la Recherche et de la Technologie, France. MRH is a recipient of a grant from Al-Hayat Hospital, Lebanon. This work was supported by INSERM (Institut National de la Santé Et de la Recherche Médicale).

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These two authors contributed equally to this work.

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