Phenotypes associated with this allele

• Allele Symbol: Elp1^tm1.1Id
• Allele Name: targeted mutation 1.1, Ioannis Dragatsis
• Allele ID: MGI:5297555
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Elp1^tm1.1Id/Elp1^tm1.1Id	involves: 129S1/Sv * C57BL/6 * CBA	MGI:5297557
cn2	Elp1^tm1Id/Elp1^tm1.1Id Tg(Hsp70-1-cre)6Arge/0	involves: 129S1/Sv * C57BL/6 * C57BL/6J * CBA	MGI:5444635
cx3	Elp1^tm1Id/Elp1^tm1.1Id Tg(IKBKAP*)#Sasl/0	involves: 129S1/Sv * C57BL/6N	MGI:5790680

Genotype
MGI:5297557

hm1

• Allelic Composition: Elp1^tm1.1Id/Elp1^tm1.1Id
• Genetic Background: involves: 129S1/Sv * C57BL/6 * CBA

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

Cardiovascular and brain malformations in Elp1^tm1Id/Elp1^tm1Id and Elp1^tm1.1Id/Elp1^tm1.1Id embryos

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:178070 )

• die between E10.5 and E11.5

embryo

abnormal vitelline vasculature morphology ( J:178070 )

• poorly vascularized at E10.5

absent second pharyngeal arch ( J:178070 )

• fails to develop at E10.5

embryonic growth retardation ( J:178070 )

• detectable at E8.5 and are about a day behind at E9.5 and E10.5

decreased embryo size ( J:178070 )

• at E9.5

absent lamina terminalis ( J:178070 )

• at E10.5 the lamina terminalis can not be identified

cardiovascular system

abnormal dorsal aorta morphology ( J:178070 )

• hypoplastic

abnormal cardinal vein morphology ( J:178070 )

• hypoplastic

abnormal vitelline vasculature morphology ( J:178070 )

• poorly vascularized at E10.5

abnormal cardiac outflow tract development ( J:178070 )

• misaligned at E10.5

abnormal heart development ( J:178070 )

• severe developmental defects at E10.5

• heart development does not progress further than and E8.5 like primitive heart

absent atrioventricular cushions ( J:178070 )

• lack endocardial cushions at E10.5

abnormal heart looping ( J:178070 )

• at E10.5

distended pericardium ( J:178070 )

• dilated at E10.5

pericardial effusion ( J:178070 )

• severe effusion at E11.5 accompanied by loss of heartbeat

absent heartbeat ( J:178070 )

• severe effusion at E11.5 accompanied by loss of heartbeat

nervous system

absent lamina terminalis ( J:178070 )

• at E10.5 the lamina terminalis can not be identified

abnormal brain development ( J:178070 )

• severe developmental defects at E10.5

• anterior development is particularly affected

• at E10.5 the diencephalon, midbrain and hindbrain regions resemble those in wild-type embryos at E9.25 - E9.5

abnormal forebrain development ( J:178070 )

abnormal telencephalon development ( J:178070 )

• development of the telencephalon is markedly compromised

• at E10.5 the telencephalic vesicle is poorly developed

integument

pallor ( J:178070 )

• embryos are pale at E10.5

craniofacial

absent second pharyngeal arch ( J:178070 )

• fails to develop at E10.5

growth/size/body

embryonic growth retardation ( J:178070 )

• detectable at E8.5 and are about a day behind at E9.5 and E10.5

decreased embryo size ( J:178070 )

• at E9.5

homeostasis/metabolism

pericardial effusion ( J:178070 )

• severe effusion at E11.5 accompanied by loss of heartbeat

vision/eye

absent optic vesicle ( J:178070 )

• at E10.5

Genotype
MGI:5444635

cn2

• Allelic Composition: Elp1^tm1Id/Elp1^tm1.1Id; Tg(Hsp70-1-cre)6Arge/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * C57BL/6J * CBA

mortality/aging

decreased survivor rate ( J:188923 )

• trimming litter size at birth allows 5% of mutants to survive postnatally

• of 6 surviving adults, 4 had to be sacrificed before 18 months of age and 2 survived to 22 months but with serious health problems, including ataxic gait, reduced locomotion activity, kyphosis and severe weight loss

postnatal lethality, incomplete penetrance ( J:188923 )

• all pups die during the first postnatal days from starvation as they fail to suck milk or swallow efficiently

• trimming litter size at birth allows 5% of mutants to survive postnatally

growth/size/body

abnormal fungiform papillae morphology ( J:188923 )

• mutants exhibit a reduction in the total number of fungiform papillae on the tongue at P18 compared with control littermates

• although fungiform papillae have a well-developed taste bud, their distribution, especially in the anterior portion of the tongue, is more sparse, and some of them do not appear healthy and are smaller than in controls

decreased birth body size ( J:188923 )

• majority of pups are born with about 70% the weight and size of their control littermates

decreased birth weight ( J:188923 )

• majority of pups are born with about 70% the weight and size of their control littermates

decreased body weight ( J:188923 )

• at P18-P21, mutants are approximately 32% the weight of wild-type littermates

• mutants over 11 months of age display low body weight

slow postnatal weight gain ( J:188923 )

decreased body length ( J:188923 )

• mutants over 11 months of age are short in length (about 85-90% the length of control littermates)

fetal growth retardation ( J:188923 )

• starting at mid-gestation, embryos have a reduced growth rate

behavior/neurological

absent gastric milk in neonates ( J:188923 )

• newborn pups lack milk in stomachs

abnormal suckling behavior ( J:188923 )

• poor sucking and uncoordinated swallow at birth

excessive scratching ( J:188923 )

• adult mutants exhibit self-inflicted wounds from frequent scratching

increased grooming behavior ( J:188923 )

• adult mutants exhibit excessive grooming, self-inflicted wounds from frequent scratching

limb grasping ( J:188923 )

• hindlimb clasping on tail suspension in mutants surviving to adulthood

abnormal posture ( J:188923 )

• P18-P21 mutants exhibit postural instability

• mutants surviving to adulthood exhibit an abnormal postural behavior (sitting-up) not observed in controls, most likely to compensate for the kyphoscoliosis

abnormal locomotor coordination ( J:188923 )

• P18-P21 mutants exhibit poor locomotor coordination

ataxia ( J:188923 )

• ataxic gait in mutants surviving to adulthood

abnormal gait ( J:188923 )

• P18-P21 mutants exhibit unsteady gait

increased thermal nociceptive threshold ( J:188923 )

• mutants exhibit decreased temperature perception, with mutants staying on a hot plate at higher temperatures than controls

• however, the discomfort caused by temperature perception tests leads to an exaggerated nocifensive response in mutants, with mutants jumping high multiple times and this behavior persists after the noxious stimulus has ceased, unlike in controls, indicating that while mutants show decreased temperature perception, they show exaggerated responses once they feel the pain

environmentally induced seizures ( J:188923 )

• handling-induced seizures in mutants surviving to adulthood

audiogenic seizures ( J:188923 )

• loud startling noise induced seizures in mutants that survive to adulthood

digestive/alimentary system

abnormal fungiform papillae morphology ( J:188923 )

• mutants exhibit a reduction in the total number of fungiform papillae on the tongue at P18 compared with control littermates

• although fungiform papillae have a well-developed taste bud, their distribution, especially in the anterior portion of the tongue, is more sparse, and some of them do not appear healthy and are smaller than in controls

abnormal intestine physiology ( J:188923 )

• mutant pups exhibit bubbles of air in their intestines at P13 indicating intestinal dysfunction

embryo

abnormal spongiotrophoblast layer morphology ( J:188923 )

• spongiotrophoblast layer is poorly developed at late gestation

• however the labyrinthine zone appears normal

small placenta ( J:188923 )

• placenta is small and thin at E16.5

abnormal placenta development ( J:188923 )

• placenta growth is impaired, averaging 55% the size of wild-type placenta in embryos from mid-gestation onwards

adipose tissue

decreased total body fat amount ( J:188923 )

• mutant pups have almost no fat content at death

• mutants surviving to over 11 months of age display very little fat content

craniofacial

abnormal fungiform papillae morphology ( J:188923 )

• mutants exhibit a reduction in the total number of fungiform papillae on the tongue at P18 compared with control littermates

• although fungiform papillae have a well-developed taste bud, their distribution, especially in the anterior portion of the tongue, is more sparse, and some of them do not appear healthy and are smaller than in controls

immune system

conjunctivitis ( J:188923 )

• 66.7% of mutants exhibit blepharoptosis and conjunctivitis with increasing age

limbs/digits/tail

abnormal autopod morphology ( J:188923 )

• mutants exhibit puffy feet at P18

nervous system

environmentally induced seizures ( J:188923 )

• handling-induced seizures in mutants surviving to adulthood

audiogenic seizures ( J:188923 )

• loud startling noise induced seizures in mutants that survive to adulthood

abnormal sympathetic ganglion morphology ( J:188923 )

• decrease in volume of sympathetic ganglia at birth (45% of controls)

abnormal stellate ganglion morphology ( J:188923 )

• at E18.5, fetuses show a significant reduction in the volume of stellate ganglia compared to controls

abnormal superior cervical ganglion morphology ( J:188923 )

• at E18.5, fetuses show a significant reduction in the volume of superior cervical sympathetic ganglia (SCG) compared to controls

• however, localization and differentiation of sympathetic neurons in superior cervical, stellate, and celiac ganglia are normal and neuronal density and neuronal numbers are not reduced at E18.5

abnormal optic nerve innervation ( J:188923 )

• decrease in the convergence of retinal ganglion cells to the optic nerve in 22 month old mutants

neurogenic bladder ( J:188923 )

♂ • urine retention/neurogenic bladder (bladder distension) and/or hydronephrosis is seen in 5 out of 17 adult males starting at 11 months of age, with partial or complete destruction of one of the kidneys in some

optic neuropathy ( J:188923 )

abnormal sensory ganglion morphology ( J:188923 )

abnormal dorsal root ganglion morphology ( J:188923 )

• decrease in volume of the dorsal root ganglion (45% of controls)

abnormal lumbar dorsal root ganglion morphology ( J:188923 )

• at 18 months of age, relative proportion of small dark B cells in lumbar dorsal root ganglia is extremely reduced compared to controls

renal/urinary system

neurogenic bladder ( J:188923 )

♂ • urine retention/neurogenic bladder (bladder distension) and/or hydronephrosis is seen in 5 out of 17 adult males starting at 11 months of age, with partial or complete destruction of one of the kidneys in some

hydronephrosis ( J:188923 )

♂ • urine retention/neurogenic bladder and/or hydronephrosis is seen in 5 out of 17 adult males starting at 11 months of age, with partial or complete destruction of one of the kidneys in some

distended urinary bladder ( J:188923 )

♂ • urine retention/neurogenic bladder (bladder distension) and/or hydronephrosis is seen in 5 out of 17 adult males starting at 11 months of age, with partial or complete destruction of one of the kidneys in some

skeleton

abnormal skeleton morphology ( J:188923 )

• 100% of mutants surviving to adulthood develop skeletal abnormalities, mostly kyphosis or kyphoscoliosis that worsens over time

kyphosis ( J:188923 )

kyphoscoliosis ( J:188923 )

vision/eye

conjunctivitis ( J:188923 )

• 66.7% of mutants exhibit blepharoptosis and conjunctivitis with increasing age

abnormal optic nerve innervation ( J:188923 )

• decrease in the convergence of retinal ganglion cells to the optic nerve in 22 month old mutants

optic neuropathy ( J:188923 )

blepharoptosis ( J:188923 )

• 66.7% of mutants exhibit blepharoptosis and conjunctivitis with increasing age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Riley-Day syndrome		DOID:11589	OMIM:223900	J:188923

Genotype
MGI:5790680

cx3

• Allelic Composition: Elp1^tm1Id/Elp1^tm1.1Id; Tg(IKBKAP*)#Sasl/0
• Genetic Background: involves: 129S1/Sv * C57BL/6N

mortality/aging

decreased survivor rate ( J:229459 )

• about 60% of mice survive postnatally; these mice have a normal life span

growth/size/body

abnormal fungiform papillae morphology ( J:229459 )

• mice exhibit fewer fungiform papillae at 4 weeks, and 3, 6, and 12 months of age

abnormal gustatory papilla taste bud morphology ( J:229459 )

• although fungiform papillae of tongues have taste buds, they are smaller with abnormal morphology and less sensory innervation

decreased birth body size ( J:229459 )

decreased body weight ( J:229459 )

• aged mice are about 70% the weight of controls

decreased body length ( J:229459 )

• aged mice are about 90% the length of controls

postnatal growth retardation ( J:229459 )

• reduction in growth rate

decreased fetal size ( J:229459 )

• smaller at E18.5, with shorter body lengths

decreased fetal weight ( J:229459 )

• reduced body weight at E18.5

adipose tissue

decreased total body fat amount ( J:229459 )

• mice have very little fat content

decreased epididymal fat pad weight ( J:229459 )

behavior/neurological

increased grooming behavior ( J:229459 )

• mice show excessive grooming after weaning (P28)

limb grasping ( J:229459 )

• hindlimb clasping that becomes severe over time

ataxia ( J:229459 )

• ataxic gait after weaning

craniofacial

abnormal fungiform papillae morphology ( J:229459 )

• mice exhibit fewer fungiform papillae at 4 weeks, and 3, 6, and 12 months of age

abnormal gustatory papilla taste bud morphology ( J:229459 )

• although fungiform papillae of tongues have taste buds, they are smaller with abnormal morphology and less sensory innervation

digestive/alimentary system

abnormal fungiform papillae morphology ( J:229459 )

• mice exhibit fewer fungiform papillae at 4 weeks, and 3, 6, and 12 months of age

abnormal gustatory papilla taste bud morphology ( J:229459 )

• although fungiform papillae of tongues have taste buds, they are smaller with abnormal morphology and less sensory innervation

embryo

small placenta ( J:229459 )

nervous system

abnormal stellate ganglion morphology ( J:229459 )

• the volume of stellate ganglia is already reduced at E18.5

• however, neuronal density in stellate ganglia is not different at E18.5

small superior cervical ganglion ( J:229459 )

• a large fraction of superior cervical ganglia are smaller and vacuolated, with the average volume about 50% that of controls by 18 months of age

• the volume of superior cervical ganglia is already reduced at E18.5

• however, neuronal density in superior cervical is not different at E18.5, indicating postntal degeneration

superior cervical ganglion degeneration ( J:229459 )

• reduction in neuronal numbers at 18 months of age

abnormal sensory neuron innervation pattern ( J:229459 )

• density of epidermal nerve fibers in the plantar hind paws of 12 month old mice is reduced, indicating reduced cutaneous sensory innervation of hind paw skin

• decrease in sensory innervation to taste buds

abnormal dorsal root ganglion morphology ( J:229459 )

• the volumes of the dorsal root ganglia are already reduced at E18.5

• the number of trkA/calcitonin gene-related peptide (CGRP) positive nociceptive neurons are reduced in the dorsal root ganglia at E18.5

abnormal lumbar dorsal root ganglion morphology ( J:229459 )

• the relative proportion of small dark B cells in lumbar dorsal root ganglia is reduced at 12 months of age while the proportion of A cells is increased

neurodegeneration ( J:229459 )

• neurodegeneration, in particular in sympathetic ganglia, occurs mainly postnatally

skeleton

kyphosis ( J:229459 )

• the Cobb angle (formed by the intersection of two lines plotted at the end-vertebrae of the curve deformity) is increased in 6 month old mice

• however, obvious skeletal malformations are not seen at E18.5

delayed bone ossification ( J:229459 )

• slight delay in ossification is seen at E18.5, particularly a delay in ossification of parietal and intraparietal cranial bones and in the phalanges

taste/olfaction

abnormal gustatory papilla taste bud morphology ( J:229459 )

• although fungiform papillae of tongues have taste buds, they are smaller with abnormal morphology and less sensory innervation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Riley-Day syndrome		DOID:11589	OMIM:223900	J:229459