Transgenic expression of testis-specific protein Y-encoded-like 2 triggers developmental and behavioral changes

Abstract

Neuronal apoptosis is an indispensable process for normal development of the central nervous system. During neonatal brain development, cell death occurs in neurons which re-enter the cell cycle but the triggering mechanism remains unknown. Proteins of the nucleosome assembly protein (NAP) family have been implicated in the control of the cell cycle. Here we raised antibodies against Testis-Specific Protein Y-encodedlike 2 (Tspyl2), a novel protein with a NAP domain, and found that Tspyl2 is ubiquitously expressed in the neonatal brain with mostly cytoplasmic and some nuclear staining. Interestingly, neurons which exhibited apoptotic features also expressed Tspyl2 in the nucleus. In transgenic mice with brain-specific overexpression of human TSPYL2, more cells entered the cell cycle and underwent apoptosis during neonatal brain development. A recent report has shown that Tspyl2 is widely expressed in the adult brain and the protein level of Tspyl2 in cultured neurons is regulated by synaptic activities (Wang, 2004. Neuron 42:113). Our transgenic mice died with a dehydrated appearance at weaning age, but could be rescued with hydrated food. Our data suggest a role of Tspyl2 in controlling neuronal loss during normal brain development. Furthermore, the transgenic animals are useful for further investigation on the role of Tspyl2 in neuronal function. [The work described in this paper was substantially supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. HKU7323/03M).]