Phenotypes Associated with This Genotype

Genotype
MGI:6369967

• Allelic Composition: Dnaaf2^{tm1.1(KOMP)Vlcg}/Dnaaf2^{tm1.1(KOMP)Vlcg}
• Genetic Background: B6N(Cg)-Dnaaf2^{tm1.1(KOMP)Vlcg}/J
• Cell Lines: 11515B-H12

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:278736 )

• embryos are grossly retarded and malformed by E8.5-9.5 and die at later stages (E11.5 and 13.5); no embryos are recovered at time of delivery

• Background Sensitivity: following breeding onto an ICR background, no newborns are obtained at N5 but embryos show better developmental progress and can be recovered at later stages

embryonic lethality, complete penetrance ( J:279207 )

• embryos are recovered at lower than expected Mendelian ratios at E7.5 (15% versus 25%) and embryonic growth is stalled by E8.5; no homozygous embryos are recovered at E9.5

embryo

absent vitelline blood vessels ( J:278736 )

• at E9.5 and E11.5, embryos fail to establish a vascular network in the yolk sac

increased embryonic tissue cell apoptosis ( J:278736 )

• at E8.5, TUNEL-positive cells accumulate in the embryonic portion

increased tail bud apoptosis ( J:278736 )

• at E9.5, TUNEL-positive cells accumulate at the tail region, unlike in control embryos

abnormal embryo development ( J:279207 )

• embryos show pleiotropic defects

• however, gastrulation occurs with anterior-posterior specification

failure of initiation of embryo turning ( J:278736 )

• embryos do not initiate embryonic turning

abnormal left-right axis patterning ( J:278736 , J:279207 )

• left-right axis specification is disrupted likely due to a malfunction of nodal cilia (J:278736)

• at E8.5 and E9.5, Pitx2 (normally expressed in the left lateral plate mesoderm) is mis-expressed in the right lateral plate mesoderm in 25% of embryos (J:278736)

• at E9.5, Hand1 (normally expressed at the outer curvature of the left ventricle) is mis-expressed on the opposite side in all embryos (J:278736)

• however, Shh is normally expressed in the notochord at E8.5 and E9.5 (J:278736)

• left-right patterning defects are observed (J:279207)

caudal body truncation ( J:278736 )

• at E9.5, the posterior axis is shortened due to cells undergoing apoptosis at the posterior end

embryonic growth arrest ( J:278736 , J:279207 )

• embryos fail to progress beyond E9.5 (early organogenesis) (J:278736)

• embryonic growth is stalled by E8.5 (J:279207)

embryonic growth retardation ( J:278736 )

• embryos show a significant developmental delay as early as gastrulation stages E6.5-7.5 and are grossly retarded by E8.5-9.5

decreased embryo size ( J:279207 )

• embryos are smaller than controls at E7.5

abnormal neural tube closure ( J:278736 )

• most embryos exhibit abnormal neural tube closure, esp. at E9.5

abnormal primitive node morphology ( J:278736 )

• although a visible node cannot be observed at E7.5, a morphological distinct node appears at ~E8.5 but is small in size and less defined relative to that in control embryos

• however, formation and extension of the primitive streak is normal at ~E6.5

decreased embryonic cilium number ( J:278736 )

• although Arl13b/T (brachyury) double-positive cells indicating cilia are present at E8.5, the node contains significantly fewer Arl13b-positive cells, consistent with decreased node size

abnormal tail bud morphology ( J:278736 )

• at E11.5, the tail bud region exhibits an abnormal cavity

growth/size/body

embryonic growth retardation ( J:278736 )

• embryos show a significant developmental delay as early as gastrulation stages E6.5-7.5 and are grossly retarded by E8.5-9.5

decreased embryo size ( J:279207 )

• embryos are smaller than controls at E7.5

cardiovascular system

absent vitelline blood vessels ( J:278736 )

• at E9.5 and E11.5, embryos fail to establish a vascular network in the yolk sac

abnormal direction of heart looping ( J:278736 )

• at E9.5, heart looping is reversed

pericardial edema ( J:278736 )

• at E11.5

nervous system

increased neural tube apoptosis ( J:278736 )

• at E9.5, TUNEL-positive cells accumulate at the neural tube, unlike in control embryos

abnormal neural tube closure ( J:278736 )

• most embryos exhibit abnormal neural tube closure, esp. at E9.5

limbs/digits/tail

abnormal tail bud morphology ( J:278736 )

• at E11.5, the tail bud region exhibits an abnormal cavity

homeostasis/metabolism

pericardial edema ( J:278736 )

• at E11.5

cellular

decreased embryonic cilium number ( J:278736 )

• although Arl13b/T (brachyury) double-positive cells indicating cilia are present at E8.5, the node contains significantly fewer Arl13b-positive cells, consistent with decreased node size

increased embryonic tissue cell apoptosis ( J:278736 )

• at E8.5, TUNEL-positive cells accumulate in the embryonic portion

increased tail bud apoptosis ( J:278736 )

• at E9.5, TUNEL-positive cells accumulate at the tail region, unlike in control embryos

increased neural tube apoptosis ( J:278736 )

• at E9.5, TUNEL-positive cells accumulate at the neural tube, unlike in control embryos

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
primary ciliary dyskinesia 10		DOID:0110612	OMIM:612518	J:278736