Phenotypes Associated with This Genotype

Genotype
MGI:5705622

• Allelic Composition: Pcnt^{Gt(RRU388)Byg}/Pcnt^{Gt(RRU388)Byg}
• Genetic Background: B6.129P2-Pcnt^{Gt(RRU388)Byg}

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:226309 )

• death at E17.5 associated with cardiovascular anomalies

growth/size/body

cleft palate ( J:226309 )

• in 50-100% of mutant embryos

abnormal head shape ( J:226309 )

kidney cyst ( J:226309 )

• glomerular and ductal cysts in 50-100% of mutant embryos

kidney cortex cyst ( J:226309 )

renal glomerulus cyst ( J:226309 )

microcephaly ( J:226309 )

prenatal growth retardation ( J:226309 )

• intrauterine growth retardation (35% smaller than wild-type controls)

cardiovascular system

abnormal vascular development ( J:226309 )

• increased density of vascular plexuses in the head and abdomen at E11.5

• variable structural and hemodynamic cardiovascular defects from E11.5 to E17.5

abnormal heart morphology ( J:226309 )

• variable structural heart defects

overriding aortic valve ( J:226309 )

abnormal heart septum morphology ( J:226309 )

• misoriented divisions are significantly increased in the developing cardiac septum at E12.5, and occur concomitantly with misdirected growth of the septum

atrial septal defect ( J:226309 )

• atrial septal defects at E17.5

atrioventricular septal defect ( J:226309 )

• atrioventricular septal defects from E11.5 to E17.5

ventricular septal defect ( J:226309 )

increased heart ventricle size ( J:226309 )

• at E17.5

hemorrhage ( J:226309 )

• whole-body hemorrhaging from E11.5 to E17.5

intracranial hemorrhage ( J:226309 )

• intracranial hemorrhaging from E11.5 to E17.5

mitral valve regurgitation ( J:226309 )

• abnormal mitral valve regurgitation at E15.5

aortic valve regurgitation ( J:226309 )

• abnormal aortic regurgitation E17.5

congestive heart failure ( J:226309 )

craniofacial

abnormal craniofacial development ( J:226309 )

cleft palate ( J:226309 )

• in 50-100% of mutant embryos

abnormal head shape ( J:226309 )

digestive/alimentary system

cleft palate ( J:226309 )

• in 50-100% of mutant embryos

homeostasis/metabolism

hydrops fetalis ( J:226309 )

• in 50-100% of mutant embryos

limbs/digits/tail

polydactyly ( J:226309 )

• hindlimb and forelimb polydactyly in 50-100% of mutant embryos

syndactyly ( J:226309 )

nervous system

intracranial hemorrhage ( J:226309 )

• intracranial hemorrhaging from E11.5 to E17.5

abnormal neuron differentiation ( J:226309 )

• low level expression of MAP2 (a phenotypic marker for differentiated neurons) in E17 mutant cortex and hippocampus, suggesting a delay in neuronal differentiation and/or neurogenesis defects

• reduced neuron-specific TUJ1 staining in E17 mutant neuroepithelium where nascent neurons arise

abnormal embryonic neuroepithelium morphology ( J:226309 )

• reduced neuron-specific TUJ1 staining in E17 mutant neuroepithelium where nascent neurons arise

abnormal brain development ( J:226309 )

• defective brain development at E17

thin cortical plate ( J:226309 )

abnormal cortical ventricular zone morphology ( J:226309 )

• significant increase in asymmetric divisions at the ventricular zone at E13.5

decreased brain size ( J:226309 )

• microcephalic brains at E17

enlarged brain ventricles ( J:226309 )

• enlarged cerebral ventricles at E17

abnormal hippocampus morphology ( J:226309 )

• severe dysplasia of hippocampus at E17

thin cerebral cortex ( J:226309 )

• thinning of the cerebral cortex at E17

renal/urinary system

abnormal kidney morphology ( J:226309 )

• variable structural kidney defects

kidney cyst ( J:226309 )

• glomerular and ductal cysts in 50-100% of mutant embryos

kidney cortex cyst ( J:226309 )

renal glomerulus cyst ( J:226309 )

duplex kidney ( J:226309 )

• duplicated kidney in 50-100% of mutant embryos

respiratory system

pulmonary hypoplasia ( J:226309 )

atelectasis ( J:226309 )

• lung atelectasis in 50-100% of mutant embryos

decreased surfactant secretion ( J:226309 )

• lack of lung surfactant in 50-100% of mutant embryos

vision/eye

abnormal eye morphology ( J:226309 )

• variable eye defects

microphthalmia ( J:226309 )

• in 50-100% of mutant embryos

• seen in one or both eyes

anophthalmia ( J:226309 )

• seen in one or both eyes

skeleton

misaligned sternebrae ( J:226309 )

• misaligned sternum ribs in 50-100% of mutant embryos

cellular

abnormal mitotic spindle morphology ( J:226309 )

• asymmetric spindles and misoriented divisions are significantly increased in mutant microcephalic brains and developing hearts

• in primary mutant MEFs, mitotic spindles show spindle misorientation and a ~4-fold decrease in both astral microtubule (MT) immunofluorescence intensity and MT length between spindle pole and cortex relative to wild-type MEFs

• the spindle angle relative to the cell-substrate adhesion plane in ~80% of mutant MEFs is >10 degrees, whereas spindles in wild-type MEFs are largely (~50%) parallel to the substratum (0 degrees)

• a unique set of centrosome proteins (ninein, Cep215, centriolin) are nearly lost from mitotic spindle poles in mutant MEFs

abnormal neuron differentiation ( J:226309 )

• low level expression of MAP2 (a phenotypic marker for differentiated neurons) in E17 mutant cortex and hippocampus, suggesting a delay in neuronal differentiation and/or neurogenesis defects

• reduced neuron-specific TUJ1 staining in E17 mutant neuroepithelium where nascent neurons arise

embryo

abnormal embryonic neuroepithelium morphology ( J:226309 )

• reduced neuron-specific TUJ1 staining in E17 mutant neuroepithelium where nascent neurons arise

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
microcephalic osteodysplastic primordial dwarfism type II		DOID:0060609	OMIM:210720	J:226309