Phenotypes associated with this allele

• Allele Symbol: Elovl4^tm1Wked
• Allele Name: targeted mutation 1, Wojciech Kedzierski
• Allele ID: MGI:3711216
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Elovl4^tm1Wked/Elovl4^tm1Wked	involves: 129S/SvEv * 129S1/Sv	MGI:3711533
ht2	Elovl4^tm1Wked/Elovl4^+	involves: 129S/SvEv * 129S1/Sv	MGI:3711534
cx3	Elovl4^tm1Wked/Elovl4^tm1Wked Tg(IVL-Elovl4)#Wked/0 Tg(KRT14-Elovl4)#Mpag/0	involves: 129 * C57BL/6	MGI:6360310

Genotype
MGI:3711533

hm1

• Allelic Composition: Elovl4^tm1Wked/Elovl4^tm1Wked
• Genetic Background: involves: 129S/SvEv * 129S1/Sv

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

mortality/aging

neonatal lethality, complete penetrance ( J:121481 )

♀ • all mice die 6 to 12 hours after birth

behavior/neurological

lethargy ( J:121481 )

♀

nervous system

abnormal synaptic vesicle exocytosis ( J:277065 )

• hippocampal neurons show faster pre-synaptic release of FM1-43 dye due to selective acceleration of synaptic vesicle fusion in a subset of synapses

abnormal synaptic vesicle number ( J:277065 )

• the recycling synaptic vesicle pool is smaller in mutant synapses than in wild-type synapses

• however, hippocampal neuronal cultures from E18.5 embryos form glutamatergic and GABAergic synapses with no overt differences from wild-type neuronal cultures

homeostasis/metabolism

impaired skin barrier function ( J:121481 )

♀

integument

impaired skin barrier function ( J:121481 )

♀

abnormal epidermal layer morphology ( J:121481 )

♀ • acylceramides are completely lacking from the epidermis

abnormal epidermis stratum corneum morphology ( J:121481 )

♀ • compacted and lacking the laminations present in wild-type

reddish skin ( J:121481 )

♀

cellular

abnormal synaptic vesicle exocytosis ( J:277065 )

• hippocampal neurons show faster pre-synaptic release of FM1-43 dye due to selective acceleration of synaptic vesicle fusion in a subset of synapses

Genotype
MGI:3711534

ht2

• Allelic Composition: Elovl4^tm1Wked/Elovl4⁺
• Genetic Background: involves: 129S/SvEv * 129S1/Sv

vision/eye

abnormal retina pigment epithelium morphology ( J:121481 )

♀ • at 9 months of age there is an abnormal accumulation of the lipofuscin component N-retinylidene-N-retinylethanolamine (A2E) precursors (87% more A2PE-H and 31% more A2PE)

abnormal rod electrophysiology ( J:121481 )

♀ • at 8 months of age, mice a reduced rod amplitude (100+/-19 compared to 164+/-33 in wild-type)

abnormal vision ( J:121481 )

♀ • reduced vision

pigmentation

abnormal retina pigment epithelium morphology ( J:121481 )

♀ • at 9 months of age there is an abnormal accumulation of the lipofuscin component N-retinylidene-N-retinylethanolamine (A2E) precursors (87% more A2PE-H and 31% more A2PE)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Stargardt disease		DOID:0050817	OMIM:248200 OMIM:600110 OMIM:603786	J:121481

Genotype
MGI:6360310

cx3

• Allelic Composition: Elovl4^tm1Wked/Elovl4^tm1Wked; Tg(IVL-Elovl4)#Wked/0; Tg(KRT14-Elovl4)#Mpag/0
• Genetic Background: involves: 129 * C57BL/6

mortality/aging

postnatal lethality, complete penetrance ( J:277065 )

• mice die by P21

growth/size/body

decreased body weight ( J:277065 )

• mice have half the body weight of wild-type mice at P20

postnatal growth retardation ( J:277065 )

• mice are developmentally delayed, with un-opened eyes and half the body weight of wild-type mice at P20

behavior/neurological

seizures ( J:277065 )

• mice develop epileptic seizures that increase in frequency until their death at P21

homeostasis/metabolism

abnormal energy homeostasis ( J:277065 )

• brains show a 3-fold increase in ATP with no significant change in other intermediary metabolites indicating increased energy demand in the brain

• however, no differences in blood-brain barrier permeability are seen

nervous system

seizures ( J:277065 )

• mice develop epileptic seizures that increase in frequency until their death at P21

abnormal nervous system electrophysiology ( J:277065 )

• mice show aberrant hippocampal neuronal firing patterns under spontaneous and evoked conditions

abnormal CNS synaptic transmission ( J:277065 )

• synaptic I/O ratios show enhanced synaptic transmission in hippocampal slices

abnormal excitatory postsynaptic potential ( J:277065 )

• when pre-synaptic release is synchronized, mutant neurons generate a larger positive fEPSP amplitude response than wild-type and the magnitude of this difference is much larger downstream in CA3 and CA1 than in the dentate gyrus

vision/eye

delayed eyelid opening ( J:277065 )

• mice have un-opened eyes at P20

cellular

increased cellular glucose import ( J:277065 )

• nearly 3-fold increase in glucose uptake in the brain, indicating increased metabolic demand in the brain

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
lipid metabolism disorder		DOID:3146		J:277065