Phenotypes Associated with This Genotype

Genotype
MGI:3615667

• Allelic Composition: Del(19Poll-Dcpd)1Nmt/Del(19Poll-Dcpd)1Nmt
• Genetic Background: involves: 129P2/OlaHsd

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

mortality/aging

premature death ( J:75779 )

• homozygotes exhibit a decline in postnatal survival, such that ~70% die by 9 weeks

postnatal lethality, incomplete penetrance ( J:75779 )

• homozygotes are obtained at the expected Mendelian ratio at E18.5; however, about 50% of homozygotes die by 3 weeks of age

nervous system

abnormal ependyma motile cilium morphology ( J:75779 )

• cilia from the respiratory epithelium and ependymal cell layer of mutant mice fail to adopt a 9+2 microtubule arrangement and lack the inner dynein arms

hydrocephaly ( J:75779 )

• all homozygotes appear to develop hydrocephalus within the first few days after birth

dilated lateral ventricle ( J:75779 )

• starting at P1, a small number of mutant pups exhibit a slight enlargement of the lateral ventricles in the presence of normal cortical neuronal development

• by 4 weeks after birth, homozygotes display severe dilatation of the lateral ventricles in the absence of gross developmental CNS defects

dilated third ventricle ( J:75779 )

• at 4 weeks, homozygotes show a moderately dilated third ventricle accompanied by ependymal hyperplasia in some mice

abnormal cerebral aqueduct morphology ( J:75779 )

• at 4 weeks, some homozygotes display ependymal hyperplasia of the cerebral aqueduct; however, no total obstruction in the cerebrospinal fluid pathway is observed

thin cerebral cortex ( J:75779 )

• at 4 weeks, homozygotes exhibit significantly thinned cerebral cortices

craniofacial

domed cranium ( J:75779 )

• by 2 to 4 weeks of age, homozygotes display dome-shaped heads

growth/size/body

megacephaly ( J:75779 )

• by 2 to 4 weeks of age, homozygotes display enlarged heads

postnatal growth retardation ( J:75779 )

• at 4 weeks, homozygotes with hydrocephalus exhibit notable growth retardation relative to wild-type littermates

situs inversus ( J:75779 )

• 5 of 26 homozygotes exhibit situs inversus totalis with reversal of the abdominal organs, heart, lungs, and aorta after removal of the liver

skeleton

domed cranium ( J:75779 )

• by 2 to 4 weeks of age, homozygotes display dome-shaped heads

reproductive system

asthenozoospermia ( J:75779 )

♂ • mutant spermatozoa exhibit no motility but able to generate offspring by direct injection into oocytes

abnormal spermatogenesis ( J:75779 )

♂ • at 7 weeks, the mutant corpus epididymis contains immature sperm with snaggy tails, residual bodies, and basophilic monocuclear cells in the lumen

teratozoospermia ( J:75779 )

♂ • at 9 weeks, mutant spermatozoa exhibit truncated and snaggy tails

globozoospermia ( J:75779 )

♂ • at 9 weeks, mutant sperm exhibit round-shaped heads

abnormal spermatid morphology ( J:75779 )

♂ • no mature spermatids are detected at stage VIII of spermatogenesis; however, the meiotic recombination step in the maturation process of spermatids is unaffected

male infertility ( J:75779 )

♂ • mutant males display normal sexual behavior but are sterile as a result of spermatozoal immobility

immune system

sinus inflammation ( J:75779 )

• homozygotes develop chronic suppurative sinusitis with accumulation of polymorphonuclear leukocytes in the nasal cavity and inflammatory cell infiltration, consisting of plasma cells and angiogenesis in the submucosal regions of the tunica mucosa olfactoria

respiratory system

abnormal respiratory motile cilium morphology ( J:75779 )

• cilia from the respiratory epithelium and ependymal cell layer of mutant mice fail to adopt a 9+2 microtubule arrangement and lack the inner dynein arms

sinus inflammation ( J:75779 )

• homozygotes develop chronic suppurative sinusitis with accumulation of polymorphonuclear leukocytes in the nasal cavity and inflammatory cell infiltration, consisting of plasma cells and angiogenesis in the submucosal regions of the tunica mucosa olfactoria

cellular

cellular phenotype ( J:75779 )

N • mutant ES cells show no significant differences in sensitivity to X-ray irradiation, UV irradiation, hydrogen peroxide or methylmethane sulfonate relative to wild-type ES cells

abnormal ependyma motile cilium morphology ( J:75779 )

• cilia from the respiratory epithelium and ependymal cell layer of mutant mice fail to adopt a 9+2 microtubule arrangement and lack the inner dynein arms

abnormal respiratory motile cilium morphology ( J:75779 )

• cilia from the respiratory epithelium and ependymal cell layer of mutant mice fail to adopt a 9+2 microtubule arrangement and lack the inner dynein arms

teratozoospermia ( J:75779 )

♂ • at 9 weeks, mutant spermatozoa exhibit truncated and snaggy tails

globozoospermia ( J:75779 )

♂ • at 9 weeks, mutant sperm exhibit round-shaped heads

abnormal spermatid morphology ( J:75779 )

♂ • no mature spermatids are detected at stage VIII of spermatogenesis; however, the meiotic recombination step in the maturation process of spermatids is unaffected

asthenozoospermia ( J:75779 )

♂ • mutant spermatozoa exhibit no motility but able to generate offspring by direct injection into oocytes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
primary ciliary dyskinesia		DOID:9562	OMIM:PS244400	J:75779