Phenotypes Associated with This Genotype

Genotype
MGI:5444514

• Allelic Composition: Elp1^tm1.2Id/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 20% of mutants to survive postnatally

• 15 of 28 (54%) of mutants survive past 18 months of age, and 7 of these live up to 22-24 months of age with minor health problems

perinatal lethality, incomplete penetrance ( J:188923 )

• approximately 95% die perinatally

• trimming litter size at birth allows 20% 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 )

decreased body size ( J:188923 )

decreased body weight ( J:188923 )

• mutants weigh 70-80% the weight of control littermates at P21

• mutants over 11 months of age also 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)

postnatal growth retardation ( J:188923 )

• postnatal growth is compromised, with mutants 70-80% the weight of control littermates at P21

fetal growth retardation ( J:188923 )

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

behavior/neurological

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

limb grasping ( J:188923 )

• hindlimb clasping on tail suspension in mutants surviving to adulthood

ataxia ( J:188923 )

• ataxic gait in mutants surviving to adulthood

abnormal posture ( J:188923 )

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

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 )

• 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 P18 indicating intestinal dysfunction

embryo

abnormal placenta development ( J:188923 )

• placenta growth is impaired, averaging 75% the size of wild-type placenta in embryos from mid-gestation onwards

adipose tissue

decreased total body fat amount ( J:188923 )

• mutants over 11 months of age have 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 )

• 40% of mutants exhibit blepharoptosis and conjunctivitis with increasing age

nervous system

environmentally induced seizures ( J:188923 )

• handling-induced seizures in mutants surviving to adulthood

audiogenic seizures ( J:188923 )

• startling noise induced seizures in mutants that survive to adulthood

abnormal muscle spindle morphology ( J:188923 )

• muscle spindles appear to develop normally but exhibit significantly reduced primary sensory afferent innervation

abnormal sympathetic ganglion morphology ( J:188923 )

• decrease in volume of sympathetic ganglia at birth (70% 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

• at P21, total volume of SCG is about 80% the volume of controls and neuronal cells are less densely packed

• by 10 months of age, both volume and neuronal density of sCGs are significantly reduced, with the volume of SCG being as low as 30% of controls

• however, localization and differentiation of sympathetic neurons in superior cervical, stellate, and celiac ganglia are normal

abnormal innervation pattern to muscle ( J:188923 )

• muscle spindles exhibit significantly reduced primary sensory afferent innervation

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 2 out of 3 adult males starting at 11 months of age, with partial or complete destruction of one of the kidneys in some

abnormal optic disk morphology ( J:188923 )

• the optic nerve head is excavated in 22 month old mutants

optic neuropathy ( J:188923 )

optic nerve atrophy ( J:188923 )

• the optic nerve head is excavated in 22 month old mutants and the retinal ganglion cell layer appears thinner

abnormal sensory ganglion morphology ( J:188923 )

abnormal dorsal root ganglion morphology ( J:188923 )

• decrease in volume of the dorsal root ganglion (70% of controls)

abnormal lumbar dorsal root ganglion morphology ( J:188923 )

• mutants exhibit a small but significant decrease in the relative proportion of small dark B cells in lumbar dorsal root ganglia at 18 months of age

abnormal autonomic nervous system physiology ( J:188923 )

• with increasing age, mutants exhibit phenotypes related to dysautonomia

renal/urinary system

neurogenic bladder ( J:188923 )

♂ • urine retention/neurogenic bladder (bladder distension) and/or hydronephrosis is seen in 2 out of 3 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 2 out of 3 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 2 out of 3 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 )

• 75% 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 )

• 40% 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

abnormal optic disk morphology ( J:188923 )

• the optic nerve head is excavated in 22 month old mutants

optic neuropathy ( J:188923 )

optic nerve atrophy ( J:188923 )

• the optic nerve head is excavated in 22 month old mutants and the retinal ganglion cell layer appears thinner

blepharoptosis ( J:188923 )

• 40% of mutants exhibit blepharoptosis and conjunctivitis with increasing age

thin retina ganglion layer ( J:188923 )

• seen in 22 month old mutants

muscle

abnormal muscle spindle morphology ( J:188923 )

• muscle spindles appear to develop normally but exhibit significantly reduced primary sensory afferent innervation

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