Extra-Neurological Characterization of Seckel Syndrome-Model Mice Harboring CEP152 Variants

Centrosomal protein 152 (CEP152) is a key regulator of centriole architecture and function, essential for proper cell division and polarity. Pathogenic variants in CEP152 cause Seckel syndrome (SCKL), a systemic disorder characterized by microcephalic primordial dwarfism. However, the mechanisms underlying its multi-organ manifestations remain poorly understood. To investigate this, we utilized two mouse models harboring patient-derived CEP152 variants, Cep152^W105*/K897* and Cep152^Q32P/Q32P. While our previous work focused on neurodevelopmental defects, here we systematically analyzed extra-neuronal phenotypes. We identified impaired spermatogenesis, characterized by defective mitosis and increased apoptosis in spermatogonia, as well as hematological abnormalities indicative of macrocytic anemia. In addition, we found reduced expression of Opalin, a gene involved in oligodendrocyte differentiation, and decreased numbers of Olig2-positive oligodendrocytes, suggesting broader glial deficits beyond recently characterized neuronal abnormalities. Collectively, our results highlight the role of CEP152 dysfunction in multi-systemic abnormalities of SCKL and provide an integrative view of its impact on both neuronal and extra-neuronal development.