Summary SPOC1 (PHF13) is a recently identified protein that has been shown to dynamically associate with somatic chromatin, to modulate chromatin compaction and to be important for proper cell division. Here, we report on the expression of SPOC1 in promyelocytic leukaemia zinc finger (PLZF)-positive undifferentiated spermatogonial stem cells (SSCs) of the mouse testis. To investigate further the biological function of SPOC1 in germ cells we generated Spoc1 mutant mice from a gene-trap embryonic stem cell clone. Postpubertal homozygous Spoc1 2/2 animals displayed a pronounced progressive loss of germ cells from an initially normal germ epithelium of the testis tubules leading to testis hypoplasia. This loss first affected non-SSC stages of germ cells and then, at a later time point, the undifferentiated spermatogonia. Remarkably, successive loss of all germ cells (at .20 weeks of age) was preceded by a transient increase in the number of undifferentiated A aligned (A al ) spermatogonia in younger mice (at .10 weeks of age). The number of primary Spoc1 2/2 gonocytes, the proliferation of germ cells, and the initiation and progression of meiosis was normal, but we noted a significantly elevated level of apoptosis in the Spoc1 2/2 testis. Taken together, the data argue that SPOC1 is indispensable for stem cell differentiation in the testis and for sustained spermatogenesis.

In order to identify novel genes involved in mental retardation/intellectual disability, we focused on a microdeletion reported in a patient with a mild form of Wolf-Hirschhorn syndrome. This patient presented with attention-deficit hyperactivity disorder, some learning and fine motor deficits as well as facial abnormalities. The deleted region included three genes. Here, we report the first characterization of one of these genes, C4ORF48. C4ORF48 encodes a short (139 aa) evolutionarily conserved protein with a predicted signal peptide and two potential dibasic convertase cleavage sites. In mice, we demonstrated expression of the corresponding protein exclusively in brain tissue using an anti-mouse C4Orf48 polyclonal antibody. Detailed RNA in situ hybridization experiments revealed expression of C4Orf48 in different zones during cortical and cerebellar development, as well as in almost all cortical and subcortical regions of the adult mouse brain. Based on the present data, we propose that C4Orf48 probably encodes a novel neuropeptide, which, if hemizygously deleted, may be involved in the observed intellectual and fine motor disabilities and thus in the overall neurological aspects of Wolf-Hirschhorn syndrome.

Summary SPOC1 (PHF13) is a recently identified protein that has been shown to dynamically associate with somatic chromatin, to modulate chromatin compaction and to be important for proper cell division. Here, we report on the expression of SPOC1 in promyelocytic leukaemia zinc finger (PLZF)-positive undifferentiated spermatogonial stem cells (SSCs) of the mouse testis. To investigate further the biological function of SPOC1 in germ cells we generated Spoc1 mutant mice from a gene-trap embryonic stem cell clone. Postpubertal homozygous Spoc1 2/2 animals displayed a pronounced progressive loss of germ cells from an initially normal germ epithelium of the testis tubules leading to testis hypoplasia. This loss first affected non-SSC stages of germ cells and then, at a later time point, the undifferentiated spermatogonia. Remarkably, successive loss of all germ cells (at .20 weeks of age) was preceded by a transient increase in the number of undifferentiated A aligned (A al ) spermatogonia in younger mice (at .10 weeks of age). The number of primary Spoc1 2/2 gonocytes, the proliferation of germ cells, and the initiation and progression of meiosis was normal, but we noted a significantly elevated level of apoptosis in the Spoc1 2/2 testis. Taken together, the data argue that SPOC1 is indispensable for stem cell differentiation in the testis and for sustained spermatogenesis.