Phenotypes Associated with This Genotype

Genotype
MGI:8248892

• Allelic Composition: Del(11Hnf1b-Znhit3)11Moro/+
• Genetic Background: involves: C57BL/6N * CD-1

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

mortality/aging

premature death ( J:334297 )

• on a 50% or greater B6N background, many of the mice that survive to P21 subsequently die or are euthanized at ~6-8 weeks because of head malformation related complications

• Background Sensitivity: on a >97% CD-1 background (achieved by outcrossing 50% B6N:50% CD-1 background F1 males onto CD-1 for F5+ generations), only 3 of 130 mice (2.3%) die or require euthanasia after weaning: one female died of unknown causes, one female was euthanized for malocclusion, and one male was euthanized for hydrocephaly

preweaning lethality, incomplete penetrance ( J:334297 )

• only a small number of mice survive to weaning (P21) on a 50% or 75% B6N background

• Background Sensitivity: a greater proportion of mice (33%) survive to P21 with increasing %s of CD-1 genetic background (75% CD-1 or >97% CD-1)

lethality during fetal growth through weaning, incomplete penetrance ( J:334297 )

• on a 75% or greater B6N background, mice are present at expected Mendelian ratios from E7 to E14, but the number of viable mice drops around birth, suggesting that lethality occurs between late prenatal (after E14) and early postnatal stages

• Background Sensitivity: no significant perinatal lethality is observed on a predominantly CD-1 background

growth/size/body

decreased embryo size ( J:334297 )

• on a 75% or greater B6N background, E8.5-E10.5 embryos are smaller than wild type embryos

• however, this difference is mostly resolved by E12.5, esp. in mildly affected embryos

decreased body weight ( J:334297 )

• on a >97% CD-1 background, 6- to 8-week-old males and females weigh significantly less than wild-type controls

abnormal head morphology ( J:334297 )

• on a 75% or greater B6N background, newborn (PO) male pups frequently show more severe head phenotypes than PO female pups where head phenotypes are more mild or moderate

abnormal jaw morphology ( J:334297 )

• on a 75% or greater B6N background, moderate P0 abnormalities include asymmetry of the mandible/maxilla

abnormal mandible morphology ( J:334297 )

• on a 75% or greater B6N background, moderate P0 abnormalities include an asymmetric lower jaw while severe P0 phenotypes include lack of mandibular fusion

abnormal maxilla morphology ( J:334297 )

• on a 75% or greater B6N background, moderate P0 abnormalities include overt asymmetry of the maxilla while severe P0 phenotypes include incomplete closure of the maxilla

abnormal nasal bone morphology ( J:334297 )

• on a 75% or greater B6N background, moderate P0 abnormalities include asymmetric nasal bones angled away from the midline

• on a >97% CD-1 background, a subset of adult (6- to 8-week-old) mice with severe frontonasal defects exhibit left or right asymmetry of the nasal bones; nasal asymmetry is more frequent in males than in females

short nasal bone ( J:334297 )

• on a 75% or greater B6N background, mild P0 abnormalities include shortened nasal bones

depressed nasal bridge ( J:334297 )

• on a >97% CD-1 background, a subset of adult (6- to 8-week-old) mice with severe frontonasal defects exhibit a depressed nasal bridge; nasal depression is more frequent in females than in males

• however, mildly affected adult CD-1 mice show no nasal abnormalities

short snout ( J:334297 )

• on a 75% or greater B6N background, mild P0 head phenotypes include a shortened snout

flat head ( J:334297 )

• on a 75% or greater B6N background, very severe P0 head phenotypes include a flattened head and hematoma protrusion

abnormal head development ( J:334297 )

• on a 75% or greater B6N background, all embryos show a range of mild to severe head anomalies during the critical window of head development (E8.5 to E12.5) but no gross abnormalities in their body plan

• by E12.5, mildly affected embryos show a discernible head structure that continues to form, whereas more severely affected embryos show a dramatically unstructured head

facial asymmetry ( J:334297 )

• on a 75% or greater B6N background, a subset of P0 pups exhibit moderate phenotypes including asymmetry of the nasal bones/misalignment with the mandible

abnormal anterior head development ( J:334297 )

• on a 75% or greater B6N background, all head structures anterior to the pharyngeal arches are disproportionately reduced in size relative to the rest of the embryo at E8.5

• in contrast, hindbrain structures are mostly unaffected

decreased body length ( J:334297 )

♀ • on a >97% CD-1 background, 6- to 8-week-old females, but not males, show a significantly lower body length than wild-type controls

postnatal growth retardation ( J:334297 )

♂ • on a >97% CD-1 background, males show a significantly lower growth rate than wild-type controls between postnatal weeks 2 and 3; in females, the growth curve diverges from that of wild-type females by week 6, but the effect of genotype on weight gain is not significant

nervous system

abnormal neural tube closure ( J:334297 )

• on a 75% or greater B6N background, very severe P0 abnormalities include incomplete closure of the neural tube

abnormal neuromere morphology ( J:334297 )

• on a >97% CD-1 background, the relative volumes of the prosomere (thalamus, periaqueductal grey), mesomere (midbrain, inferior colliculus, superior colliculus) and ventricular region are increased, respectively, by 1.6%, 1.8% and 4.4%

abnormal brain development ( J:334297 )

• on a 75% or greater B6N background, E8.5 to E12.5 embryos show a range of brain anomalies; at E9.5, the prosencephalon and mesencephalon are reduced, whereas the rhombencephalon begins to develop more normally

• at E12.5, mildly affected B6N embryos show abnormal or abrogated partitioning or maturation of the brain vesicles, whereas more severely affected embryos lack vesicle distinctions

• at P0, very severely affected B6N pups show profound brain anomalies, including lack of differentiation, incomplete closure of the neural tube, protrusions through the skull, and lack of all forebrain structures

abnormal forebrain development ( J:334297 )

• on a 75% or greater B6N background, a subset of mildly and severely affected embryos show deficient forebrain development at E8.5

abnormal telencephalon development ( J:334297 )

• on a 75% or greater B6N background, a subset of severely affected embryos show absence or severe malformation of the telencephalon at E10.5 and E12.5; mildly affected embryos show deficient and/or underdeveloped but present telencephalic vesicles at E10.5

absent embryonic telencephalon ( J:334297 )

• on a 75% or greater B6N background, a subset of severely affected embryos show absence of the telencephalon at E10.5 and E12.5

abnormal hindbrain development ( J:334297 )

• on a 75% or greater B6N background, a subset of severely affected embryos show profound malformation and/or under-differentiation of the hindbrain at E10.5 and E12.5

abnormal midbrain development ( J:334297 )

• on a 75% or greater B6N background, a subset of severely affected embryos show profound malformation and/or under-differentiation of the midbrain at E10.5 and E12.5

abnormal midbrain-hindbrain boundary morphology ( J:334297 )

• on a >97% CD-1 background, the relative volume of the isthmus (including the cerebellum) in adult males is significantly increased by 4%

abnormal midbrain-hindbrain boundary development ( J:334297 )

• on a 75% or greater B6N background, the invagination of the midbrain-hindbrain isthmic organizer, indicating the anterior metencephalon, is less distinct in severely affected embryos at E10.5

increased hindbrain size ( J:334297 )

• on a 75% or greater B6N background, a subset of mildly and severely affected embryos show an increased relative rhombencephalon size at E8.5

decreased brain size ( J:334297 )

• on a 75% or greater B6N background, mildly and moderately affected P0 pups show reduced brain size

• on a >97% CD-1 background, the MRI brain volume in adult males trends lower than that of wild-type controls by 2.2%

enlarged brain ventricles ( J:334297 )

• on a 75% or greater B6N background, moderately affected P0 brains show extreme ventricular dilatation

abnormal midbrain morphology ( J:334297 )

• on a 75% or greater B6N background, a subset of mildly and severely affected embryos show an abnormality in mesencephalic structure or size at E9.5

decreased midbrain size ( J:334297 )

• on a 75% or greater B6N background, the mesencephalon is clearly reduced in size at E9.5; by E10.5, the mesencephalon is variably affected depending on the severity of the overall phenotype

absent tectum ( J:334297 )

• on a 75% or greater B6N background, a subset of mildly affected and delayed/severely affected embryos show absence of clear tectum mesencephali at E8.5

abnormal forebrain morphology ( J:334297 )

• on a 75% or greater B6N background, a subset of mildly and severely affected embryos show an abnormality in prosencephalic structure or size at E9.5

• on a >97% CD-1 background, the relative MRI volume of the rostral secondary prosencephalon (including the hypothalamus and mammillary bodies) in adult males is significantly increased by 2.3%

decreased forebrain size ( J:334297 )

• on a 75% or greater B6N background, the prosencephalon is clearly reduced in size at E9.5

abnormal diencephalon morphology ( J:334297 )

• on a 75% or greater B6N background, a subset of severely affected embryos show absence or severe malformation of the diencephalon at E10.5 and E12.5

abnormal hypothalamus morphology ( J:334297 )

• on a >97% CD-1 background, the MRI relative volume of the adult male hypothalamus is increased by 3.5%

absent diencephalon ( J:334297 )

• on a 75% or greater B6N background, a subset of severely affected embryos show absence of the diencephalon at E10.5 and E12.5

abnormal telencephalon morphology ( J:334297 )

• on a >97% CD-1 background, the relative volumes of the dorsal pallium (comprising most of the cerebral cortex) and ventral pallium (comprising the olfactory bulb, endopiriform and piriform cortex) in adult males are significantly reduced by 1.3% and 7.2%, respectively

dilated lateral ventricle ( J:334297 )

• on a >97% CD-1 background, adult males with no nasal abnormalities exhibit mild lateral ventricular dilatation, whereas adult males with either nasal bone asymmetry or nasal bridge depression show severe lateral ventricular dilatation

• adult female CD-1 mice with no nasal abnormalities exhibit only a few structural abnormalities, whereas adult females with either nasal bone asymmetry or nasal bridge depression show asymmetric lateral ventricle dilatation

abnormal cerebral hemisphere morphology ( J:334297 )

• on a 75% or greater B6N background, severe P0 abnormalities include unilateral malformations of the cortical hemispheres

abnormal hippocampus development ( J:334297 )

• on a 75% or greater B6N background, mild and moderate P0 abnormalities include hollow cortical structures, indicating deficient hippocampal genesis

decreased corpus callosum size ( J:334297 )

• on a >97% CD-1 background, adult males with severe lateral ventricular dilatation show thinning of the corpus callosum

hippocampus hypoplasia ( J:334297 )

• on a 75% or greater B6N background, moderately affected P0 brains show hippocampal hypoplasia

abnormal cerebral cortex morphology ( J:334297 )

• on a 75% or greater B6N background, mild and moderate P0 abnormalities include hollow cortical structures; severe cases show profound malformations and asymmetric underdevelopment of the cortex, including abnormal vascularization

thin cerebral cortex ( J:334297 )

• on a 75% or greater B6N background, moderately affected P0 brains show a thinned cerebral cortex

• on a >97% CD-1 background, adult males with severe lateral ventricular dilatation show thinning of the posterior cortex; adult females with asymmetric lateral ventricle dilatation show asymmetric posterior cortical thinning

abnormal auditory cortex morphology ( J:334297 )

• on a >97% CD-1 background, the MRI absolute volume of the adult male primary auditory cortex is reduced by 6.3%

abnormal olfactory bulb morphology ( J:334297 )

• on a 75% or greater B6N background, moderate P0 abnormalities include asymmetric olfactory bulbs

abnormal olfactory bulb layer morphology ( J:334297 )

• on a >97% CD-1 background, the MRI absolute volumes of the five olfactory bulb layers (glomerular, external plexiform, mitral cell, internal plexiform, granule cell) are significantly smaller in adult males by an average of 15%

abnormal olfactory tract morphology ( J:334297 )

• on a >97% CD-1 background, the MRI absolute volume of the adult male lateral olfactory tract is reduced by 9%

abnormal septal nucleus morphology ( J:334297 )

• on a >97% CD-1 background, the MRI relative volumes of the medial and lateral septa in adult males are increased, respectively, by 6.7% and 8.3%

absent forebrain ( J:334297 )

• on a 75% or greater B6N background, very severe P0 abnormalities include lack of all forebrain structures

abnormal metencephalon morphology ( J:334297 )

• on a 75% or greater B6N background, a subset of mildly affected embryos show underdevelopment of the metencephalon but presence of the isthmus at E10.5; the invagination of the midbrain-hindbrain isthmic organizer, indicating the anterior metencephalon, is less distinct in severely affected embryos

abnormal ansiform lobule crus I morphology ( J:334297 )

• on a >97% CD-1 background, the MRI absolute volume of the cerebellar crus I of the ansiform lobule in adult males is reduced by 6%

increased cerebellum fastigial nucleus size ( J:334297 )

• on a >97% CD-1 background, the MRI relative volume of the adult male cerebellar fastigial nucleus is increased by 7%

craniofacial

abnormal cranium morphology ( J:334297 )

• on a 75% or greater B6N background, severe P0 abnormalities include incomplete closure of the skull; very severe cases show protrusions through the skull

abnormal jaw morphology ( J:334297 )

• on a 75% or greater B6N background, moderate P0 abnormalities include asymmetry of the mandible/maxilla

abnormal mandible morphology ( J:334297 )

• on a 75% or greater B6N background, moderate P0 abnormalities include an asymmetric lower jaw while severe P0 phenotypes include lack of mandibular fusion

abnormal maxilla morphology ( J:334297 )

• on a 75% or greater B6N background, moderate P0 abnormalities include overt asymmetry of the maxilla while severe P0 phenotypes include incomplete closure of the maxilla

abnormal nasal bone morphology ( J:334297 )

• on a 75% or greater B6N background, moderate P0 abnormalities include asymmetric nasal bones angled away from the midline

• on a >97% CD-1 background, a subset of adult (6- to 8-week-old) mice with severe frontonasal defects exhibit left or right asymmetry of the nasal bones; nasal asymmetry is more frequent in males than in females

short nasal bone ( J:334297 )

• on a 75% or greater B6N background, mild P0 abnormalities include shortened nasal bones

domed cranium ( J:334297 )

• on a 75% or greater B6N background, mild P0 head phenotypes include a domed skull

abnormal nasal pit morphology ( J:334297 )

• on a 75% or greater B6N background, a subset of mildly affected embryos show underdevelopment of the olfactory pit at E10.5

facial asymmetry ( J:334297 )

• on a 75% or greater B6N background, a subset of P0 pups exhibit moderate phenotypes including asymmetry of the nasal bones/misalignment with the mandible

depressed nasal bridge ( J:334297 )

• on a >97% CD-1 background, a subset of adult (6- to 8-week-old) mice with severe frontonasal defects exhibit a depressed nasal bridge; nasal depression is more frequent in females than in males

• however, mildly affected adult CD-1 mice show no nasal abnormalities

short snout ( J:334297 )

• on a 75% or greater B6N background, mild P0 head phenotypes include a shortened snout

flat head ( J:334297 )

• on a 75% or greater B6N background, very severe P0 head phenotypes include a flattened head and hematoma protrusion

embryo

decreased embryo size ( J:334297 )

• on a 75% or greater B6N background, E8.5-E10.5 embryos are smaller than wild type embryos

• however, this difference is mostly resolved by E12.5, esp. in mildly affected embryos

abnormal neural tube closure ( J:334297 )

• on a 75% or greater B6N background, very severe P0 abnormalities include incomplete closure of the neural tube

abnormal neuromere morphology ( J:334297 )

• on a >97% CD-1 background, the relative volumes of the prosomere (thalamus, periaqueductal grey), mesomere (midbrain, inferior colliculus, superior colliculus) and ventricular region are increased, respectively, by 1.6%, 1.8% and 4.4%

skeleton

abnormal cranium morphology ( J:334297 )

• on a 75% or greater B6N background, severe P0 abnormalities include incomplete closure of the skull; very severe cases show protrusions through the skull

abnormal jaw morphology ( J:334297 )

• on a 75% or greater B6N background, moderate P0 abnormalities include asymmetry of the mandible/maxilla

abnormal mandible morphology ( J:334297 )

• on a 75% or greater B6N background, moderate P0 abnormalities include an asymmetric lower jaw while severe P0 phenotypes include lack of mandibular fusion

abnormal maxilla morphology ( J:334297 )

• on a 75% or greater B6N background, moderate P0 abnormalities include overt asymmetry of the maxilla while severe P0 phenotypes include incomplete closure of the maxilla

abnormal nasal bone morphology ( J:334297 )

• on a 75% or greater B6N background, moderate P0 abnormalities include asymmetric nasal bones angled away from the midline

• on a >97% CD-1 background, a subset of adult (6- to 8-week-old) mice with severe frontonasal defects exhibit left or right asymmetry of the nasal bones; nasal asymmetry is more frequent in males than in females

short nasal bone ( J:334297 )

• on a 75% or greater B6N background, mild P0 abnormalities include shortened nasal bones

domed cranium ( J:334297 )

• on a 75% or greater B6N background, mild P0 head phenotypes include a domed skull

respiratory system

abnormal nasal bone morphology ( J:334297 )

• on a 75% or greater B6N background, moderate P0 abnormalities include asymmetric nasal bones angled away from the midline

• on a >97% CD-1 background, a subset of adult (6- to 8-week-old) mice with severe frontonasal defects exhibit left or right asymmetry of the nasal bones; nasal asymmetry is more frequent in males than in females

short nasal bone ( J:334297 )

• on a 75% or greater B6N background, mild P0 abnormalities include shortened nasal bones

abnormal nasal pit morphology ( J:334297 )

• on a 75% or greater B6N background, a subset of mildly affected embryos show underdevelopment of the olfactory pit at E10.5

depressed nasal bridge ( J:334297 )

• on a >97% CD-1 background, a subset of adult (6- to 8-week-old) mice with severe frontonasal defects exhibit a depressed nasal bridge; nasal depression is more frequent in females than in males

• however, mildly affected adult CD-1 mice show no nasal abnormalities

vision/eye

abnormal lens development ( J:334297 )

• on a 75% or greater B6N background, a subset of mildly affected embryos show underdevelopment or absence of the lens at E12.5

abnormal lens vesicle development ( J:334297 )

• on a 75% or greater B6N background, a subset of mildly affected embryos show underdevelopment of the lens vesicle at E10.5

absent lens vesicle ( J:334297 )

• on a 75% or greater B6N background, a subset of severely affected embryos show absence of the lens vesicle at E10.5 and E12.5

abnormal optic cup morphology ( J:334297 )

• on a 75% or greater B6N background, a subset of mildly and severely affected embryos show absence of optic invagination at E8.5-E12.5

abnormal optic vesicle formation ( J:334297 )

• on a 75% or greater B6N background, a subset of mildly and severely affected embryos show absence or deficiency of the optic vesicle at E9.5

absent optic vesicle ( J:334297 )

• on a 75% or greater B6N background, a subset of mildly and severely affected embryos show absence ofthe optic vesicle at E9.5

unilateral microphthalmia ( J:334297 )

• on a 75% or greater B6N background, P0 eye abnormalities include unilateral mild or severe hypoplasia of the eye

anophthalmia ( J:334297 )

• on a 75% or greater B6N background, moderate P0 eye phenotypes include unilateral anophthalmia (absence of the right or left eye)

homeostasis/metabolism

impaired glucose tolerance ( J:334297 )

♂ • on a >97% CD-1 background, adult (6- to 8-week-old) males, but not females, show impaired blood glucose clearance in an i.p. glucose tolerance test

renal/urinary system

abnormal renal glomerulus morphology ( J:334297 )

• on a >97% CD-1 background, adult (6- to 8-week-old) males exhibit a significantly smaller mean glomerular diameter (width) than wild-type controls but this effect is only modest and non-significant in females

• a subset of adult CD-1 males and females display an increased number of immature and/or dysplastic glomeruli in the absence of gross kidney abnormalities

• however, mean glomerular number is not significantly reduced in adult male and female mice and no differences in the frequencies of tubular degeneration or mononuclear cell infiltrate are observed

cardiovascular system

hematoma ( J:334297 )

• on a 75% or greater B6N background, very severe P0 head phenotypes include a flattened head and hematoma protrusion

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:334297 )

N • on a >97% CD-1 background, 6- to 8-week-old mice show no obvious pancreas abnormalities by H&E staining

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chromosome 17q12 deletion syndrome		DOID:0060404	OMIM:614527	J:334297