Phenotypes Associated with This Genotype

Genotype
MGI:5444635

• Allelic Composition: Elp1^tm1.1Id/Elp1^tm1.2Id
• Genetic Background: involves: 129S1/Sv * C57BL/6 * C57BL/6J * CBA

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

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