Phenotypes associated with this allele

• Allele Symbol: Th^tm1Tna
• Allele Name: targeted mutation 1, Toshiharu Nagatsu
• Allele ID: MGI:1860453
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Th^tm1Tna/Th^tm1Tna	either: (involves: 129P2/OlaHsd * C57BL/6) or (involves: 129P2/OlaHsd * ICR)	MGI:2682637
ht2	Th^tm1Tna/Th^+	B6.129-Th^tm1Tna	MGI:3629513

Genotype
MGI:2682637

hm1

• Allelic Composition: Th^tm1Tna/Th^tm1Tna
• Genetic Background: either: (involves: 129P2/OlaHsd * C57BL/6) or (involves: 129P2/OlaHsd * ICR)

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

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:30273 )

• homozygotes are grossly normal up to E12.5; however, 55-57% of embryos die from E14.5 to E16.5 with a variable degree of degradation

neonatal lethality, complete penetrance ( J:30273 )

• when offspring delivered by Cesarean section are cross-fostered by breeding females, viable homozygotes appear normal within 5-6 hrs after birth but die by P1 without any structural failure in major organs

perinatal lethality, incomplete penetrance ( J:30273 )

• when delivered by Cesarean section at E18.5, 75% of homozygotes undergo resorption as a consequence of death

• 19% of homozygotes begin to breathe and turned pink within 10 min after birth; however, the remaining 6% die of anoxia within 10 min after birth

homeostasis/metabolism

abnormal adrenaline level ( J:30273 )

• at E12.5, homozygotes show no detectable adrenaline levels

• newborn homozygotes delivered by Cesarean section display very low adrenaline levels in both head and body regions

decreased dopamine level ( J:30273 )

• at E12.5, homozygotes display a dopamine level of 37.5% in the head and 7.7% in the body of wild-type levels

• newborn homozygotes delivered by Cesarean section display a dopamine level of only 23.0% in the head and 41.7% in the body of wild-type levels

abnormal noradrenaline level ( J:30273 )

• at E12.5, homozygotes show no detectable noradrenaline levels

• newborn homozygotes delivered by Cesarean section display very low noradrenaline levels in both head and body regions

anoxia ( J:30273 )

• when delivered by Cesarean section at E18.5, 6% of homozygotes die of anoxia within 10 min after birth

respiratory system

atelectasis ( J:30273 )

• homozygotes dying at birth exhibit atelectasis with no structural blockage in bronchi, bronchioles, and upper respiratory tract; however, signs of degeneration are noted in heart, liver and kidney

respiratory failure ( J:30273 )

• when delivered by Cesarean section at E18.5, 6% of homozygotes fail to breathe and respond poorly to a tapping stimulus

cardiovascular system

decreased heart rate ( J:30273 )

• newborn homozygotes delivered by Cesarean section show significant bradycardia relative to wild-type mice (210 17 bpm vs 307 9 bpm, respectively)

abnormal ST segment ( J:30273 )

• newborn homozygotes delivered by Cesarean section show a slight elevation of the S-T segment; however, no major differences in wave morphology are observed on surface electrocardiograms

Genotype
MGI:3629513

ht2

• Allelic Composition: Th^tm1Tna/Th⁺
• Genetic Background: B6.129-Th^tm1Tna

behavior/neurological

abnormal learning/memory/conditioning ( J:60963 )

• heterozygotes exhibit impairment in the water-finding task associated with latent learning performance; training fails to shorten the finding and drinking latencies, despite normal locomotor activity and exploratory behavior

• post-training latencies for both finding and drinking performances are restored by desipramine-induced stimulation of noradrenergic activity

abnormal associative learning ( J:60963 )

• heterozygotes exhibit mild impairment in long-term memory formation in three distinct forms of associative learning (active avoidance, cued fear conditioning, and conditioned taste aversion)

• associative learning deficits are restored by desipramine-induced stimulation of noradrenergic activity

• notablty, spatial learning and hippocampal long-term potentiation remain unaffected

abnormal active avoidance behavior ( J:60963 )

abnormal conditioned taste aversion behavior ( J:60963 )

abnormal cued conditioning behavior ( J:60963 )

homeostasis/metabolism

abnormal noradrenaline level ( J:60963 )

• heterozygotes show a moderate reduction of noradrenaline levels in brains regions, including the frontal cortex, midbrain, hypothalamus, hippocampus and pons medulla, to 73%-80% of wild-type levels

• measurement of extracellular noradrenaline levels in the frontal cortex by microdialysis indicates a significant reduction in high K⁺-evoked noradrenaline release