Analysis Tools
mortality/aging
|
• die by the first or second postnatal day
|
|
• many mice die shortly after birth
|
|
• die by the first or second postnatal day
|
|
• most mice die within 7 days of birth
|
renal/urinary system
|
• reduced number of cilia
|
|
• at E18.5
(J:176174)
• renal cystic dysplasia is seen by E15.5
(J:193837)
|
growth/size/body
|
• at E18.5
(J:176174)
• renal cystic dysplasia is seen by E15.5
(J:193837)
|
microcephaly
(
J:193837
)
|
• mutants with JBTS-like phenotype exhibit microcephaly or other facial dysmorphologies
|
|
• severe postnatally in rare survivors
|
nervous system
|
• 35% of E11.5 embryos exhibit a Meckel-Gruber syndrome (MKS)-like phenotype
• 58% of embryos exhibit a Joubert syndrome (JBTS)-like syndrome
• Background Sensitivity: F6-F10 filial generations on the C57BL/6J background exhibit a variable Meckel-Gruber syndrome (MKS)-like phenotype
• Background Sensitivity: F10 or more filial generations on the C57BL/6J background exhibit a less variable Joubert syndrome (JBTS)-like phenotype
• some embryos show features similar to Dandy-Walker malformation, including dilated fourth ventricle and occipital swelling behind the cerebellar hemisphere
|
|
• E11.5 mutants with the JBTS-like phenotype retain primary cilia at the neuroepithelial cell layer of the caudal neural tube, however E18.5 lateral ventricles show the presence of abnormal, bulbous cilia
|
|
• marker analysis of E11.5 mutants with the MKS-like phenotype indicates dorsalization of the neural tube
• marker analysis of E11.5 mutants with the JBTS-like phenotype indicates a mild ventralization of the neural tube
|
|
• E11.5-E14.5 mutants with the MKS-like phenotype exhibit near total loss of cilia at the developing neuroepithelium cell layer
|
|
• 4 of 17 embryos with the MKS-like phenotype have an anterior neuropore closure defect
|
meningocele
(
J:193837
)
|
• 1 of 6 embryos with the MKS-like phenotype exhibit an occipital meningocele
|
|
• the planar organization of the ependymal cell layer is disrupted in mice with both the MKS-like and JBTS-like phenotypes
|
|
• E11.5 mutants with the MKS-like phenotype exhibit a variable defect of the roof plate, including expanded roof plate
|
|
• all mutants with the MKS-like phenotype exhibit prosencephalon dysgenesis at E11.5
• mutants with JBTS-like phenotype do not exhibit an overt neural tube defect, but all mice have a smaller forebrain at E11.5 and a reduced anteroposterior axis of the developing forebrain at E15.5
|
|
• some embryos with the JBTS-like phenotype have a deep interpenduncular fossa with a reduced anterioposterior axis of the midbrain tegmentum at the level of the isthmus accompanied by cerebellar vermis hypoplasia or aplasia, features of the 'molar tooth sign'
|
|
• prosecephalon dysgenesis later manifests as semi-lobar holoprosencephaly in which the two lateral ventricles are fused with an absence of some midline structures such as the anterior commissure and variable degrees of corpus callosum dysgenesis
|
|
• some mutants have a small forebrain at E13.5-P0
|
|
• some mutants have a large forebrain at E13.5-P0
|
|
• mutants with JBTS-like phenotype have a small hindbrain region
|
|
• E11.5 mutants with MKS-like phenotype show variable dilation of the fourth ventricle
• dialted fourth ventricle is also seen in an E15.5 mutant showing Dandy-Walker malformation
|
|
• mutants with the MKS-like phenotype show variable degrees of corpus callosum dysgenesis
|
|
• in mutants with the MKS-like phenotype
|
|
• some embryos with the JBTS-like phenotype exhibit a reduced anterioposterior axis of the midbrain tegmentum at the level of the isthmus
|
|
• mice with the MKS-like phenotype exhibit enlargement of the basal ganglia
|
|
• mice with the MKS-like phenotype exhibit enlargement of the hippocampus
|
|
• some embryos with the JBTS-like phenotype show cerebellar vermis hypoplasia or aplasia
|
|
• an E15.5 mutant showing Dandy-Walker malformation exhibits a smaller and downwardly-displaced cerebellar hemisphere
|
exencephaly
(
J:193837
)
|
• 4 of 17 embryos with the MKS-like phenotype show midbrain-hindbrain exencephaly at E11.5
|
|
• from E13.5, frontal encephalocele of embryos with the MKS-like phenotype shows variable severity ranging from a mild defect of a slight protrusion in the frontal area to a gross encephalocele/meningocele-like anomaly in either a median or paramedian position
|
embryo
|
• E11.5-E14.5 mutants with the MKS-like phenotype exhibit near total loss of primary cilia at the developing neuroepithelium cell layer
• mouse embryonic fibroblasts (MEFS) from MKS-like mutants lack primary cilia or develop very short cilia in 5% of cells
|
|
• marker analysis of E11.5 mutants with the MKS-like phenotype indicates dorsalization of the neural tube
• marker analysis of E11.5 mutants with the JBTS-like phenotype indicates a mild ventralization of the neural tube
|
|
• embryos with exencephaly at E11.5 show failure of fusion of the neural folds
|
|
• marker analysis of E11.5 mutants with the MKS-like phenotype indicates dorsalization of the neural tube
• marker analysis of E11.5 mutants with the JBTS-like phenotype indicates a mild ventralization of the neural tube
|
|
• E11.5-E14.5 mutants with the MKS-like phenotype exhibit near total loss of cilia at the developing neuroepithelium cell layer
|
|
• 4 of 17 embryos with the MKS-like phenotype have an anterior neuropore closure defect
|
meningocele
(
J:193837
)
|
• 1 of 6 embryos with the MKS-like phenotype exhibit an occipital meningocele
|
|
• the planar organization of the ependymal cell layer is disrupted in mice with both the MKS-like and JBTS-like phenotypes
|
|
• E11.5 mutants with the MKS-like phenotype exhibit a variable defect of the roof plate, including expanded roof plate
|
craniofacial
|
• E15.5 embryos with JBTS-like phenotypes exhibit complex posterior fossa defects, showing dysplasia of the caudal medulla, absence of the inferior olive nucleus, deep abnormal interpeduncular fossa, abnormally dilated cisterna magna and septa, and an enlarged and protruding locus coeruleus
|
|
• P0 pups with JBTS-like phenotypes exhibit a hypoplastic mandible
|
liver/biliary system
|
• developmental defects of the biliary tree
|
cellular
| N |
• mouse embryonic fibroblasts develop cilia
|
|
• mouse embryonic fibroblasts (MEFS) from MKS-like mutants lack primary cilia or develop very short cilia in 5% of cells
• 40% of MEFs from JBTS-like mutants have abnormally long cilia
|
|
• E11.5 mutants with the JBTS-like phenotype retain primary cilia at the neuroepithelial cell layer of the caudal neural tube, however E18.5 lateral ventricles show the presence of abnormal, bulbous cilia
|
|
• E11.5-E14.5 mutants with the MKS-like phenotype exhibit near total loss of primary cilia at the developing neuroepithelium cell layer
• mouse embryonic fibroblasts (MEFS) from MKS-like mutants lack primary cilia or develop very short cilia in 5% of cells
|
|
• reduced number of cilia
|
|
• MEFs from MKS-like mutants exhibit centrosomal defects comprising widely separated mother/daughter centrosomes and multiple centrosomes
|
skeleton
|
• E15.5 embryos with JBTS-like phenotypes exhibit complex posterior fossa defects, showing dysplasia of the caudal medulla, absence of the inferior olive nucleus, deep abnormal interpeduncular fossa, abnormally dilated cisterna magna and septa, and an enlarged and protruding locus coeruleus
|
|
• P0 pups with JBTS-like phenotypes exhibit a hypoplastic mandible
|
limbs/digits/tail
| N |
• mutants do not exhibit pre-axial or post-axial polydactyly
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Joubert syndrome 6 | DOID:0111001 |
OMIM:610688 |
J:193837 | |
| Meckel syndrome | DOID:0050778 |
OMIM:PS249000 |
J:193837 | |
