Phenotypes Associated with This Genotype

Genotype
MGI:3027496

• Allelic Composition: Htr4^tm1Comp/Htr4^tm1Comp
• Genetic Background: 129/Sv-Htr4^tm1Comp

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

mortality/aging

preweaning lethality, incomplete penetrance ( J:87451 )

• only 18% of homozygotes are derived from heterozygous intercrosses over a 3-year period, indicating a small deviation from the expected Mendelian ratio

behavior/neurological

increased susceptibility to pharmacologically induced seizures ( J:87451 )

• homozygotes are hypersensitive to pentamethylenetetrazol (PTZ)-induced seizures, showing a higher number of deaths at 60 min post-treatment as well as reduced latency to both death and tonic seizure relative to wild-type controls

decreased exploration in new environment ( J:87451 )

• homozygotes are less reactive to novelty-induced locomotion in the open field than wild-type controls, showing an overall 45% decrease in traveled path length on day 1 (but not day 2 or 3) of exposure in both the periphery and center of the open field

• however, no differences in home cage locomotor activity or motor coordination (rotarod test) are observed

abnormal food intake ( J:87451 , J:125754 )

• homozygotes show an attenuated response to stress-induced hypophagia relative to wild-type controls (-19.6% vs -36.4%, respectively), exhibiting a +24% increase in food intake during the first 24 hrs after an acute restraint stress (no food/water for 110 min) but resuming normal (baseline) consumption levels at 48 hrs after stress (J:87451)

• whether fed or food-deprived, BIMU8-treated mice fail to exhibit reduced food intake unlike in wild-type mice (J:125754)

• MDMA treated mice fail to exhibit a suppression in appetite unlike wild-type mice (J:125754)

increased anxiety-related response ( J:87451 )

• homozygotes spend significantly less time in the center of an open field during day 1 and 2 (but not day 3) of exposure than wild-type controls, suggesting a slight hyperanxiety-like behavior

nervous system

increased susceptibility to pharmacologically induced seizures ( J:87451 )

• homozygotes are hypersensitive to pentamethylenetetrazol (PTZ)-induced seizures, showing a higher number of deaths at 60 min post-treatment as well as reduced latency to both death and tonic seizure relative to wild-type controls

growth/size/body

growth/size/body region phenotype ( J:87451 , J:125754 )

N • at 4 months of age, homozygotes display normal baseline eating and drinking behavior in their home cages (J:87451)

N • no differences in social behavior, aggression, or sleep are observed relative to age-matched controls (J:87451)

N • mice exhibit normal body weight after 3 days of habituation or 24 h food deprivation (J:125754)

abnormal body weight ( J:87451 )

• unlike wild-type controls, homozygotes fail to display a significant body weight loss during the first 4 days of recovery from an acute restraint stress

• however, no difference in body weight is observed between unrestrained wild-type and mutant mice during development or at 4 months of age

adipose tissue

decreased white adipose tissue amount ( J:87451 )

• after restraint stress, homozygotes display a lower white adipose tissue weight/body weight ratio than wild-type controls (-38%), with no difference in their total body weight

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:87451 )

N • no difference in corticosterone levels is noted between wild-type and mutant mice before or after the elevated plus maze

N • normal metabolic parameters (feces, urine) are observed at 4 months of age

decreased physiological sensitivity to xenobiotic ( J:125754 )

• whether fed or food-deprived, BIMU8-treated mice fail to exhibit reduced food intake unlike in wild-type mice

• MDMA treated mice fail to exhibit a suppression in appetite unlike wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
anorexia nervosa		DOID:8689		J:125754