All Phenotypes Pdcd6ip<tm1.2Adz> MGI Mouse

• both sexes are smaller than wild-type controls

domed cranium ( J:238436 )

• mice are often identified by the domed shape of their head, suggestive of hydrocephalus

abnormal brain ependyma motile cilium physiology ( J:238436 )

• abnormal positioning of the basal bodies and basal feet in the lateral wall results in altered directionality of the axonemes, asynchronous beating of the ependymal cilia, and loss of CSF vectorial flow

hydrocephaly ( J:238436 )

• starting at P8, all mice develop bilateral hydrocephalus associated with progressive build-up of cerebrospinal fluid

• however, no signs of obstruction of the Sylvius aqueduct are observed

decreased brain size ( J:238436 )

• at 1 month of age, brain volume to body weight ratio is smaller than that of wild-type controls

• however, cerebellum is of normal size and morphology

abnormal brain ependyma morphology ( J:238436 )

• beta-catenin and gamma-tubulin immunofluorescence revealed ependymal cells of irregular size and shape and abnormal positioning of the basal bodies

abnormal brain ependyma motile cilium morphology ( J:238436 )

• SEM images of the lateral wall revealed altered organization of brain ependyma motile cilia

• however, a normal 9 + 2 axoneme structure is preserved

abnormal brain ependyma motile cilium location or orientation ( J:238436 )

• SEM images of the lateral wall revealed altered orientation of brain ependyma motile cilia

• TEM analysis of the basal bodies revealed abnormally orientated basal feet, unlike in wild-type controls

enlarged lateral ventricles ( J:238436 )

• starting at P8, all mice exhibit progressive enlargement of the lateral ventricles

• however, no expansion of the fourth ventricle is observed

abnormal choroid plexus morphology ( J:238436 )

• the choroid plexus (CP) epithelial cell layer is not organized in one plane as in wild-type controls, but appears undulated with vast membrane protrusions on the apical site

• TEM analysis revealed misaligned epithelial cells of irregular shape and size, prominent blebbing of microvilli, and an abnormally distended apical junctional complex (AJC)

• SEM images of the CP apical surface showed extensive blebbing and large gaps between epithelial cells

• beta-catenin and gamma-tubulin immunofluorescence confirmed abnormal cell shape and mislocalized ciliary basal bodies of variable size not properly polarized to the apical site

• after i.p. Evans blue dye injection, a large area of leakage is seen within and around the lateral ventricles, instead of being restricted to the CP as in wild-type controls

• striking defects in the assembly and positioning of the actomyosin-tight junction polarity complex in the CP culminate in pathologic levels of cell extrusion from the epithelial layer

• 3D confocal analysis of whole-mount CP showed Tunnel+ and Myosin IIa+ cells being extruded from epithelial cell layer, unlike in wild-type controls, and increased intracellular flux of FITC-dextran into the CP that at some points co-localizes with ZO-1, a tight junction protein, suggesting loss of the epithelial barrier

small hippocampus ( J:238436 )

• reduced hippocampus size at 1 month of age

thin cerebral cortex ( J:238436 )

• thinning of the cerebral cortex at 1 month of age

astrocytosis ( J:238436 )

• mice exhibit increased GFAP immunostaining of astrocytes in the ependymal/sub-ependymal layer of the lateral walls, suggesting damage caused by increased ventricular pressure

abnormal cerebrospinal fluid flow ( J:238436 )

• starting at P8, all mice exhibit progressive build-up of cerebrospinal fluid (CSF) within the lateral ventricles

• loss of CSF vectorial flow is caused by asynchronous beating of the ependymal motile cilia

abnormal tracheal ciliated epithelium morphology ( J:238436 )

• SEM analysis of primary cultures of tracheal epithelial cells revealed that several cells are extruded from the apical site of the epithelial layer

• tracheal epithelial cells are of irregular size and shape and show abnormal distribution of CD9 (a marker of microvilli)