Phenotypes Associated with This Genotype

Genotype
MGI:3790867

• Allelic Composition: Lrp2^tm1Her/Lrp2^tm1Her
• Genetic Background: involves: 129S7/SvEvBrd

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

mortality/aging

perinatal lethality, complete penetrance ( J:34835 )

• about 50% die within the first few minutes because of an inability to breathe; the others initially ventilate normally but die from respiratory insufficiency within 2-3 hours

growth/size/body

flat forehead ( J:34835 )

• newborns show a flattened forehead

short snout ( J:34835 )

• nose is shortened in newborns

decreased embryo size ( J:34835 )

• embryos are smaller at E9.5

embryo

decreased embryo size ( J:34835 )

• embryos are smaller at E9.5

abnormal embryonic neuroepithelium morphology ( J:34835 )

• E8.5 embryos exhibit impaired epithelial cohesion resulting in uneven cobblestone-like neuroepithelial surface

delayed neural tube closure ( J:34835 )

• at E9.5, anterior neural tube closure is frequently delayed

nervous system

abnormal embryonic neuroepithelium morphology ( J:34835 )

• E8.5 embryos exhibit impaired epithelial cohesion resulting in uneven cobblestone-like neuroepithelial surface

delayed neural tube closure ( J:34835 )

• at E9.5, anterior neural tube closure is frequently delayed

abnormal forebrain development ( J:34835 )

small embryonic telencephalon ( J:34835 )

• smaller at E9.5

holoprosencephaly ( J:34835 )

• fusion of the forebrain hemispheres

• the lateral (IV) and III ventricles are frequently fused to form a common holoprosencephalic cavity in 6 of 10 mutants

abnormal choroid plexus morphology ( J:34835 )

• mutants often have a characteristic protrusion in the midline of the crown that is caused by a prolapse of the choroid plexus

abnormal telencephalon morphology ( J:34835 )

• small telencephalon with an uneven edge of the neural folds

absent corpus callosum ( J:34835 )

• absent in 9 of 10 mutants

absent olfactory bulb ( J:34835 )

• newborns show an almost invariable absence of the olfactory bulbs

exencephaly ( J:34835 )

• seen in 10 of 106 newborns

respiratory system

atelectasis ( J:34835 )

• newborns exhibit atelectic areas in the lungs

overexpanded pulmonary alveolus ( J:34835 )

abnormal respiratory system physiology ( J:34835 )

emphysema ( J:34835 )

• newborns exhibit emphysematous areas in the lungs

respiratory failure ( J:34835 )

homeostasis/metabolism

cyanosis ( J:34835 )

• about 50% of mutants remain severely cyanotic after birth and die within the first few minutes

abnormal urine homeostasis ( J:108230 )

• urine of the 2% of mutants that survive to adulthood contains increased amounts of vitamin A (retinol) and 25-OH vitamin D3

increased urine protein level ( J:108230 , J:184259 )

• the 2% of mutants that survive to adult hood exhibit renal resorption deficiency as seen by the excretion of low molecular weight plasma proteins in the urine (low molecular weight plasma proteinuria) (J:108230)

• proteins excreted include small plasma proteins that carry lipophilic compounds including vitamin D-binding protein, retinol-binding protein, alpha1-microglobulin and odorant-binding protein, indicating urinary loss of lipophilic vitamins bound to the carrier proteins (J:108230)

• adult survivors excrete vitamin D-binding protein and retinol-binding protein (J:184259)

increased urine microglobulin level ( J:108230 )

• increased urine alpha1-microglobulin level

craniofacial

abnormal viscerocranium morphology ( J:34835 )

• variable degree of frontonasal bone dysmorphology, however rest of the skeleton appears normal

flat forehead ( J:34835 )

• newborns show a flattened forehead

short snout ( J:34835 )

• nose is shortened in newborns

renal/urinary system

abnormal urine homeostasis ( J:108230 )

• urine of the 2% of mutants that survive to adulthood contains increased amounts of vitamin A (retinol) and 25-OH vitamin D3

increased urine protein level ( J:108230 , J:184259 )

• the 2% of mutants that survive to adult hood exhibit renal resorption deficiency as seen by the excretion of low molecular weight plasma proteins in the urine (low molecular weight plasma proteinuria) (J:108230)

• proteins excreted include small plasma proteins that carry lipophilic compounds including vitamin D-binding protein, retinol-binding protein, alpha1-microglobulin and odorant-binding protein, indicating urinary loss of lipophilic vitamins bound to the carrier proteins (J:108230)

• adult survivors excrete vitamin D-binding protein and retinol-binding protein (J:184259)

increased urine microglobulin level ( J:108230 )

• increased urine alpha1-microglobulin level

abnormal proximal convoluted tubule morphology ( J:34835 , J:108230 )

• decrease in the number and size of large endosomes in proximal tubular epithelial cells (reduction in the number of endocytic apical vesicles) (J:34835)

• the 2% of mutants that survive to adulthood exhibit a reduction in the number of coated pits, endosomes, and lysosomes in kidney proximal tubules (J:108230)

skeleton

abnormal viscerocranium morphology ( J:34835 )

• variable degree of frontonasal bone dysmorphology, however rest of the skeleton appears normal

vision/eye

microphthalmia ( J:34835 )

• seen in some mutants

anophthalmia ( J:34835 )

• seen in some mutants

cellular

increased apoptosis ( J:34835 )

• increase in apoptosis is seen at E9.5 in areas that correspond to regions containing facio-acoustic (VII) or trigeminal (V) neural crest, as well as around the optic vesicle

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Fanconi syndrome		DOID:1062	OMIM:PS134600	J:108230