Phenotypes associated with this allele

• Allele Symbol: Ank2^tm1Bnt
• Allele Name: targeted mutation 1, Vann Bennett
• Allele ID: MGI:2179754
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ank2^tm1Bnt/Ank2^tm1Bnt	B6.129-Ank2^tm1Bnt/Bnt	MGI:6790245
hm2	Ank2^tm1Bnt/Ank2^tm1Bnt	involves: 129	MGI:5431705
hm3	Ank2^tm1Bnt/Ank2^tm1Bnt	involves: 129X1/SvJ * C57BL/6	MGI:2181775
ht4	Ank2^tm1Bnt/Ank2^+	involves: 129	MGI:4830468

Genotype
MGI:6790245

hm1

• Allelic Composition: Ank2^tm1Bnt/Ank2^tm1Bnt
• Genetic Background: B6.129-Ank2^tm1Bnt/Bnt

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

behavior/neurological

enhanced spatial learning ( J:277752 )

♂ • slight in the acquisition phase of a Morris water maze

♂ • however, performance in the reversal phase is normal

abnormal social/conspecific interaction behavior ( J:277752 )

♂ • males make small or no territory markings in response to female urine

decreased vocalization ( J:277752 )

♂ • fewer ultrasonic vocalization

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autistic disorder		DOID:12849	OMIM:209850	J:277752

Genotype
MGI:5431705

hm2

• Allelic Composition: Ank2^tm1Bnt/Ank2^tm1Bnt
• Genetic Background: involves: 129

nervous system

nervous system phenotype ( J:186168 )

N • axon initial segments are normal

Genotype
MGI:2181775

hm3

• Allelic Composition: Ank2^tm1Bnt/Ank2^tm1Bnt
• Genetic Background: involves: 129X1/SvJ * C57BL/6

Small body size in Ank2^tm1Bnt/Ank2^tm1Bnt mouse compared to wild type

mortality/aging

postnatal lethality, complete penetrance ( J:52124 )

• 95% of remaining homozygotes die by P8; only a few (4 out of 8) survive to P20

neonatal lethality, incomplete penetrance ( J:52124 )

• over half of homozygotes are moribund (and therefore killed) at P1

behavior/neurological

impaired balance ( J:52124 )

• homozygotes that survive to 2 weeks of age exhibit impaired balance

abnormal locomotor behavior ( J:52124 )

• homozygotes that survive to 2 weeks of age exhibit abnormal locomotor activity

growth/size/body

decreased body weight ( J:52124 )

• homozygotes that survive to 2 weeks of age exhibit a 75% reduction in body weight relative to wild-type littermates

vision/eye

optic nerve degeneration ( J:52124 )

• at P9, many mutant optic nerve axons become dilated with diameters up to 8-fold greater than normal, and contain multivescicular bodies

• axon fasciculation is also impaired with frequent loss of direct axon-axon contacts

• a nearly complete degeneration of the optic nerve is noted by P21

disorganized secondary lens fibers ( J:52124 , J:70385 )

• disruption of secondary lens fiber organization at anterior pole (J:52124)

• organization of secondary lens fibers at the anterior pole was severely disturbed at postnatal day 1 (J:70385)

nervous system

enlarged lateral ventricles ( J:52124 )

• at P1, homozygotes show a 7-fold enlargement of the lateral ventricles

• enlargement of lateral ventricles is not associated with occlusion of the cerebral aqueduct

decreased corpus callosum size ( J:52124 )

• at P1-P5, ~61.5% homozygotes display a size reduction or absence of the corpus callosum; a nearly complete absence of the anterior portion is observed

• the corpus callosum cannot be visualized in parasagittal sections and appears greatly reduced in coronal sections of mutant brain

decreased brain internal capsule size ( J:52124 )

• at P1, homozygotes exhibit a size reduction or absence of the internal capsule

abnormal anterior corticospinal tract morphology ( J:52124 )

• at P1, homozygotes exhibit hypoplasia or absence of the pyramidal tracts

abnormal lateral corticospinal tract morphology ( J:52124 )

• at P1, homozygotes exhibit hypoplasia or absence of the pyramidal tracts

abnormal axon morphology ( J:52124 )

• homozygotes display decreased L1 staining in premyelinated axons of long fiber tracts, including the corpus callosum, fimbria, and internal capsule in the brain, and pyramidal tracts and lateral columns of the spinal cord

• L1 staining is unreduced in the mutant optic nerve at P1-P3 but disappears by P7, although the optic nerve itself is still present

optic nerve degeneration ( J:52124 )

• at P9, many mutant optic nerve axons become dilated with diameters up to 8-fold greater than normal, and contain multivescicular bodies

• axon fasciculation is also impaired with frequent loss of direct axon-axon contacts

• a nearly complete degeneration of the optic nerve is noted by P21

Genotype
MGI:4830468

ht4

• Allelic Composition: Ank2^tm1Bnt/Ank2⁺
• Genetic Background: involves: 129

cardiovascular system

increased heart rate variability ( J:163867 )

• in isoproterenol-treated mice

abnormal sinoatrial node conduction ( J:163867 )

• isoproterenol-treated mice exhibit disorganized shifts of the leading pacemaker and competing multiple pacemakers compared with similarly treated wild-type mice

• acetylcholine-treated mice exhibit reduced sensitivity of pacemaker function compared with similarly treated wild-type mice

homeostasis/metabolism

abnormal physiological response to xenobiotic ( J:163867 )

• isoproterenol-treated mice exhibit increased heart rate variability, a larger beat-to-beat variability, disorganized shifts of the leading pacemaker, and competing multiple pacemakers compared with similarly treated wild-type mice

• acetylcholine-treated mice exhibit reduced sensitivity of pacemaker function compared with similarly treated wild-type mice

adipose tissue

abnormal fat cell differentiation ( J:222913 )

• mouse embryonic fibroblasts exhibit increased adipogenesis with both increased in adipocyte numbers and enlarged lipid droplets compared with wild-type cells.

decreased adipocyte glucose uptake ( J:222913 )

• decreased basal adipocyte glucose uptake

• however, insulin-stimulated uptake is normal

cellular

abnormal fat cell differentiation ( J:222913 )

• mouse embryonic fibroblasts exhibit increased adipogenesis with both increased in adipocyte numbers and enlarged lipid droplets compared with wild-type cells.

decreased adipocyte glucose uptake ( J:222913 )

• decreased basal adipocyte glucose uptake

• however, insulin-stimulated uptake is normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
sinoatrial node disease		DOID:0050824		J:163867