Phenotypes associated with this allele

• Allele Symbol: Pibf1^m1Bei
• Allele Name: mutation 1, David R Beier
• Allele ID: MGI:7798750
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pibf1^m1Bei/Pibf1^m1Bei	involves: A/J	MGI:8243281
ht2	Pibf1^m1Bei/Pibf1^tm1.1(KOMP)Vlcg	involves: A/J * C57BL/6J * C57BL/6N	MGI:8243284

Genotype
MGI:8243281

hm1

• Allelic Composition: Pibf1^m1Bei/Pibf1^m1Bei
• Genetic Background: involves: A/J

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

craniofacial

cleft upper lip ( J:371501 )

• micro-CT analysis of E18.5 embryos indicates a cleft lip phenotype

growth/size/body

cleft upper lip ( J:371501 )

• micro-CT analysis of E18.5 embryos indicates a cleft lip phenotype

Genotype
MGI:8243284

ht2

• Allelic Composition: Pibf1^m1Bei/Pibf1^{tm1.1(KOMP)Vlcg}
• Genetic Background: involves: A/J * C57BL/6J * C57BL/6N

growth/size/body

micrognathia ( J:371501 )

• at E13.5

abnormal midface morphology ( J:371501 )

• frontal views of compound heterozygous embryos indicate midfacial narrowing at E15.5

midface hypoplasia ( J:371501 )

• by E11.5, maxillary hyperplasia results in midline fusion of maxillary prominences and midfacial hypoplasia

midline cleft upper lip ( J:371501 )

• at E13.5

arched palate ( J:371501 )

• compound heterozygous embryos exhibit a constricted and high-arched palate at E17.5

tongue hypoplasia ( J:371501 )

• compound heterozygous embryos exhibit hypoglossia at E13.5 and E15.5

midline facial cleft ( J:371501 )

• at E13.5

abnormal head mesenchyme morphology ( J:371501 )

• in culture, immunostaining for ARL13B (a marker of primary cilia) and gamma-TUBULIN (a centrosome marker) shows a severe reduction in the number of ciliated cells in immortalized facial mesenchyme cells, indicating impaired ciliogenesis

• moreover, immortalized facial mesenchyme cells show a nearly complete loss of PIBF1 nuclear expression

• RNAscope in frontal sections indicates broad expansion of Lhx6 expression throughout the CNCC-derived facial mesenchyme at E13.5

cardiovascular system

pericardial edema ( J:371501 )

• at E9.5

homeostasis/metabolism

pericardial edema ( J:371501 )

• at E9.5

craniofacial

micrognathia ( J:371501 )

• at E13.5

abnormal craniofacial development ( J:371501 )

• at E9.5, whole head (cranial) tissue shows a skewed ratio of GLI3FL:GLI3R (a hallmark molecular readout of a ciliopathy) as well as an indication of impaired Hedgehog (HH) signal transduction

abnormal frontonasal prominence morphology ( J:371501 )

• compound heterozygous embryos exhibit hypoplastic and anteriorly displaced frontonasal prominences at E11.5

• whole mount RNAscope indicates expanded Fgf8 expression in the epithelium of the frontonasal prominence at E9.5

frontonasal prominence hypoplasia ( J:371501 )

• at E11.5

abnormal mandibular prominence morphology ( J:371501 )

• whole mount RNAscope indicates expanded expression of Fgf8 (fibroblast growth factor 8) in 1st arch derivatives (maxillary and mandibular prominences), along with increased Lhx6 (LIM homeobox protein 6) expression adjacent to the Fgf8 domain within the mandibular prominence at E9.5

mandibular prominence hypoplasia ( J:371501 )

• at E9.5

abnormal maxillary prominence morphology ( J:371501 )

• compound heterozygous embryos exhibit midline fusion of the maxillary prominences at E11.5, E13.5 and E15.5

• whole mount RNAscope indicates expanded expression of Fgf8 (fibroblast growth factor 8) in 1st arch derivatives (maxillary and mandibular prominences), along with increased Lhx6 (LIM homeobox protein 6) expression adjacent to the Fgf8 domain within the maxillary prominence at E9.5

enlarged maxillary prominence ( J:371501 )

• compound heterozygous embryos exhibit maxillary prominence hyperplasia at E9.5 and E11.5

abnormal first pharyngeal arch morphology ( J:371501 )

• whole mount RNAscope indicates expansion of Lhx6 expression in the first branchial arch at E9.5

abnormal midface morphology ( J:371501 )

• frontal views of compound heterozygous embryos indicate midfacial narrowing at E15.5

midface hypoplasia ( J:371501 )

• by E11.5, maxillary hyperplasia results in midline fusion of maxillary prominences and midfacial hypoplasia

midline cleft upper lip ( J:371501 )

• at E13.5

arched palate ( J:371501 )

• compound heterozygous embryos exhibit a constricted and high-arched palate at E17.5

tongue hypoplasia ( J:371501 )

• compound heterozygous embryos exhibit hypoglossia at E13.5 and E15.5

midline facial cleft ( J:371501 )

• at E13.5

embryo

abnormal cranial neural crest cell migration ( J:371501 )

• increased amounts of Sox10+ cranial neural crest cells (CNCCs) are observed streaming into the frontonasal and maxillary prominences at E9.0

abnormal first pharyngeal arch morphology ( J:371501 )

• whole mount RNAscope indicates expansion of Lhx6 expression in the first branchial arch at E9.5

abnormal head mesenchyme morphology ( J:371501 )

• in culture, immunostaining for ARL13B (a marker of primary cilia) and gamma-TUBULIN (a centrosome marker) shows a severe reduction in the number of ciliated cells in immortalized facial mesenchyme cells, indicating impaired ciliogenesis

• moreover, immortalized facial mesenchyme cells show a nearly complete loss of PIBF1 nuclear expression

• RNAscope in frontal sections indicates broad expansion of Lhx6 expression throughout the CNCC-derived facial mesenchyme at E13.5

nervous system

abnormal forebrain development ( J:371501 )

• whole mount RNAscope indicates a significant decrease in Shh (sonic hedgehog) expression in the developing ventral forebrain at E9.5

abnormal telencephalon development ( J:371501 )

• telencephalic vesicles fail to fully separate even at E16.5

abnormal midbrain-hindbrain boundary development ( J:371501 )

• whole mount RNAscope indicates expanded Fgf8 expression in the midbrain-hindbrain boundary at E9.5

semilobar holoprosencephaly ( J:371501 )

• no separation between the telencephalic ventricles is noted at E11.5; however, marginal separation common to semilobar holoprosencephaly (HPE) is observed by E13.5

• HPE-like phenotypes continue to be present at E15.5 and E16.5

abnormal medial ganglionic eminence morphology ( J:371501 )

• in addition to semilobar HPE, duplication of the medial ganglionic eminence is observed at E13.5, as determined by immunofluorescent staining of NKX2.1

• RNAscope in frontal sections shows expanded Lhx6 expression within the duplicated and endogenous medial ganglionic eminence

exencephaly ( J:371501 )

• at E9.5

cellular

abnormal primary cilium morphology ( J:371501 )

• in culture, immunostaining for ARL13B (a marker of primary cilia) and gamma-TUBULIN (a centrosome marker) shows a severe reduction in the number of ciliated cells in immortalized facial mesenchyme cells, indicating impaired ciliogenesis

abnormal centrosome morphology ( J:371501 )

• cranial sections of E9.5 embryos show absence of BBS4 (Bardet-Biedl syndrome 4) co-localization with gamma-TUBULIN and significantly reduced expression of PCM1 (pericentriolar material 1) at the centrosome, indicating impaired recruitment of key pericentriolar proteins

abnormal cranial neural crest cell migration ( J:371501 )

• increased amounts of Sox10+ cranial neural crest cells (CNCCs) are observed streaming into the frontonasal and maxillary prominences at E9.0

skeleton

micrognathia ( J:371501 )

• at E13.5

vision/eye

microphthalmia ( J:371501 )

• at E13.5

digestive/alimentary system

arched palate ( J:371501 )

• compound heterozygous embryos exhibit a constricted and high-arched palate at E17.5

tongue hypoplasia ( J:371501 )

• compound heterozygous embryos exhibit hypoglossia at E13.5 and E15.5

limbs/digits/tail

polydactyly ( J:371501 )

• compound heterozygous embryos exhibit extra digits at E13.5 and E15.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Joubert syndrome 33		DOID:0080279	OMIM:617767	J:371501