Phenotypes associated with this allele

• Allele Symbol: Htr1a^tm1Rhn
• Allele Name: targeted mutation 1, Rene Hen
• Allele ID: MGI:2387407
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Htr1a^tm1Rhn/Htr1a^tm1Rhn	129S6/SvEvTac-Htr1a^tm1Rhn	MGI:3045712
hm2	Htr1a^tm1Rhn/Htr1a^tm1Rhn	involves: 129S/SvEv * 129S1/Sv	MGI:4881537
hm3	Htr1a^tm1Rhn/Htr1a^tm1Rhn	involves: 129S1/Sv	MGI:3045711
ht4	Htr1a^tm1Rhn/Htr1a^+	involves: 129S1/Sv	MGI:3045796

Genotype
MGI:3045712

hm1

• Allelic Composition: Htr1a^tm1Rhn/Htr1a^tm1Rhn
• Genetic Background: 129S6/SvEvTac-Htr1a^tm1Rhn

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

homeostasis/metabolism

increased dopamine level ( J:65662 )

• dopamine (DA) levels are increased in caudate-putamen (+55%), 3,4-dihydroxyphenylacetic acid (DOPAC) in olfactory bulb (+120%), and homovanillic acid (HVA) in substantia nigra (+59%)

• in spite of the DA and 3-methoxytyramine (3-MT) increases in caudate-putamen, DA turnover ([DA metabolites]/[DA]) remains unaltered in this region

• notably, DA turnover is significantly increased in olfactory bulb (+81%) and substantia nigra (+88%), as well as in the dorsal/medial raphe nuclei (+89%)

increased noradrenaline level ( J:65662 )

• in homozygotes, the noradrenaline (NA) content is elevated in olfactory bulb (+74%), thalamus (57%), substantia nigra (+63%), and cerebellum (+52%)

abnormal serotonin level ( J:65662 , J:70686 )

• notably, 5-hydroxyindole-3-acetic acid (5-HIAA) content is increased significantly in olfactory bulb (+193%), substantia nigra (+133%), dorsal/medial raphe nuclei (+110%), locus coeruleus (+86%), and thalamus (+47%) (J:65662)

• levels of 5-hydroxytryptophol (5-HTOL) are increased in substantia nigra (+124%), dorsal/medial raphe nuclei (+105%), and probably locus coeruleus (+61%), but not in olfactory bulb (J:65662)

• high [5-HT metabolites]/[5-HT] ratios indicate that 5-HT turnover is increased considerably in olfactory bulb (+87%), substantia nigra (+138%), dorsal/medial nuclei (+79%), and locus coeruleus (+103%) (J:65662)

• importantly, mutants show a significant reduction in density of 5-HTT binding in several brain regions, including parts of the cerebral cortex, limbic system, thalamus and basal ganglia (J:70686)

nervous system

nervous system phenotype ( J:65662 , J:70686 )

N • homozygotes show only a few significant differences in regional serotonin concentration throughout the brain and spinal cord (J:65662)

N • homozygous mutants do not display any compensatory changes in HTR1B density (J:70686)

N • homozygotes have a normal density of serotonin transporter (5-HTT) binding in the raphe nuclei, i.e. in serotonin somata/dendrites (J:70686)

Genotype
MGI:4881537

hm2

• Allelic Composition: Htr1a^tm1Rhn/Htr1a^tm1Rhn
• Genetic Background: involves: 129S/SvEv * 129S1/Sv

behavior/neurological

increased anxiety-related response ( J:167655 )

nervous system

abnormal nervous system physiology ( J:167655 )

• in the elevated plus maze and open field, mutants exhibit a larger increase in medial prefrontal cortex theta power than wild-type mice

• however, no differences in theta power in the ventral or dorsal hippocampus are observed

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
anxiety disorder		DOID:2030	OMIM:607834	J:167655

Genotype
MGI:3045711

hm3

• Allelic Composition: Htr1a^tm1Rhn/Htr1a^tm1Rhn
• Genetic Background: involves: 129S1/Sv

behavior/neurological

behavioral despair ( J:51280 )

• in the forced swim test, homozygotes are significantly more active than wild-type, particularly during the last 10 min of the test

• homozygotes appear to display less behavioral despair than wild-type littermates; whereas wild-type mice become progressively more immobile, homozygous mutants maintain the same level of activity throughout the swim test

increased anxiety-related response ( J:51280 )

• in the open field, homozygotes exhibit decreased exploratory activity and increased anxious-like behavior relative to wild-type

• in the elevated plus maze, homozygotes display significantly more anxiety-like behaviors with no significant changes in activity

• homozygous null males appear to be affected more than females, particularly in some measures of anxiety

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
anxiety disorder		DOID:2030	OMIM:607834	J:51280

Genotype
MGI:3045796

ht4

• Allelic Composition: Htr1a^tm1Rhn/Htr1a⁺
• Genetic Background: involves: 129S1/Sv

behavior/neurological

increased anxiety-related response ( J:51280 )

• relative to homozygotes, heterozygotes, which express ~50% of wild-type receptor density, display intermediate phenotypes in most behavioral tests