Phenotypes Associated with This Genotype

Genotype
MGI:7867699

• Allelic Composition: Adnp^em1Goz/Adnp⁺
• Genetic Background: C57BL/6N-Adnp^em1Goz

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

mortality/aging

neonatal lethality, incomplete penetrance ( J:361953 )

• a lower number of pups survive at postnatal day 1 (43% versus the expected 50%)

behavior/neurological

impaired long-term object recognition memory ( J:361953 )

♂ • adult naive males (not exposed to foster dams/handling) show long-term memory impairment in the novel object recognition test

increased grooming behavior ( J:361953 )

• adult mice show increased grooming frequency

• males, but not females, show increased grooming duration

abnormal reflex ( J:361953 )

• pups gain the reflex for cliff aversion sooner than wild-type pups

abnormal suckling reflex ( J:361953 )

• NAP treated pups gain the rooting reflex later than NAP treated wild-type pups

• however, rooting reflex is not different in untreated mice

abnormal pinna reflex ( J:361953 )

• pups acquire the ear twitch reflex earlier than wild-type pups

abnormal righting response ( J:361953 )

• surviving pups show delayed surface-righting (pup righting on all 4 paws on a flat surface) and air-righting (righting to the correct orientation midair) indicating delayed acquisition of vestibular reflexes

• treatment with NAP corrects the delayed righting response/vestibular reflexes in pups

abnormal startle reflex ( J:361953 )

• pups gain the auditory startle reflex significantly later than wild-type pups

impaired coordination ( J:361953 )

♀ • females show decreased latency to fall in the hanging wire test

abnormal gait ( J:361953 )

• both males and females exhibit a smaller front base of support

• females, but not males, exhibit slower swing speed with increased duration

• NAP treatment partially corrects the smaller front base of support in males but not in females and corrects the slower swing speed and increased duration in females

long stride length ( J:361953 )

♂ • males, but not females, exhibit an increase in footprint length and area

♂ • NAP treatment corrects this increase in footprint length and area

decreased thermal nociceptive threshold ( J:361953 )

• mice show decreased latency to nociception in the hot plate

impaired social recognition ( J:361953 )

• adult naive mice show impaired social recognition

abnormal vocalization ( J:361953 )

• mice show decreased vocalization syntax complexity

• NAP treatment improves the syntax complexity

decreased vocalization ( J:361953 )

• mice show decreased total ultrasonic vocalization during pup-dam separation

• however, NAP treatment has no effect on the decreased vocalization

digestive/alimentary system

abnormal gut flora balance ( J:361953 )

• males exhibit an increase in total eubacterial load, Bifidobacterium genus, and Lactobacillus group, as well as decreased loads of Enterobacteriaceae

• females exhibit an increase in bacterial load of Bifidobacterium

• treatment with the microtubule/autophagy-protective ADNP fragment NAPVSIPQ (NAP) restores normal levels of total eubacterial load and normalizes the increased bacterial load of Bifidobacterium in females

growth/size/body

decreased body weight ( J:361953 )

♀ • female, but not male, pups are lighter from P10

♀ • NAP treatment restores normal weight, visible from P10 and reaching significance at P20-21

decreased body length ( J:361953 )

♀ • female, but not male, pups are shorter from P10

hearing/vestibular/ear

abnormal hearing physiology ( J:361953 )

• mice show differences in ear twitch, cliff aversion, and auditory startle reflexes, suggesting delayed hearing

nervous system

tau protein deposits ( J:361953 )

♂ • 2-month-old males show hyperphosphorylated tau deposits in the hippocampus and visual cortex

♂ • NAP treatment ameliorates the hyperphosphorylated tau deposits in the hippocampus and visual cortex

decreased dendritic spine density ( J:361953 )

• males exhibit an approximate 15% reduction in CA1 hippocampal dendritic spine density

• females exhibit an approximate 16% reduction in spine density in the motor cortex L5 layer

• NAP treatment ameliorates this reduction in dendritic spine density

abnormal synapse morphology ( J:361953 )

♀ • females exhibit an approximate 25% decrease in PSD95 volume in the hippocampus (representing immature synapses)

♀ • NAP treatment ameliorates this reduction in PSD95 volume

taste/olfaction

abnormal olfaction ( J:361953 )

• mice exhibit impaired odor discrimination

• NAP treatment reverses the odor discrimination impairment in females but not males

vision/eye

delayed eyelid opening ( J:361953 )

♀ • females, but not males, exhibit delayed eye opening

♀ • NAP treatment reverses the delay in eye opening

abnormal visual evoked potential ( J:361953 )

♂ • males exhibit abnormal visual evoked potentials

♂ • NAP treatment reverses abnormalities of visual evoke potentials at all stimulation intensities tested except for the 100 mcd of the P3 waveform

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Helsmoortel-Van Der Aa Syndrome		DOID:0070058	OMIM:615873	J:361953