Phenotypes Associated with This Genotype

Genotype
MGI:2670622

• Allelic Composition: Hap1^tm1Hay/Hap1^tm1Hay
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * ICR

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

mortality/aging

postnatal lethality, complete penetrance ( J:76174 )

• although homozygotes are born at the expected Mendelian frequency, >70% die within 2 days of birth primarily due to diminished feeding and malnutrition

• no homozygotes survive beyond 8 days of life

behavior/neurological

abnormal eating behavior ( J:76174 )

• by P2, homozygotes display an obvious decrease in feeding behavior, despite normal balance and motor coordination at P1-P6 and a normal suckling behavior at P1-P4

• feeding, weight gain and survival can not be improved by trimming the litter between P1-P2 to remove almost all of competing control littermates

• other physiological processes including sensitivity to tactile stimuli and mild pain remain normal

absent gastric milk in neonates ( J:76174 )

• by P2, homozygotes contain little to no milk in their stomachs

growth/size/body

decreased body size ( J:76174 )

• at P1, homozygotes are slightly smaller than wild-type and heterozygous littermates

• by P3, live homozygotes are dramatically smaller than control littermates

decreased body weight ( J:76174 )

• at P1, >94% of homozygous mutant pups weigh less than 1.60 g, whereas 44% of wild-type and 48% of heterozygous controls weigh more than 1.60 g

• however, no gross anatomical abnormalities are noted in the heart, liver, lungs, adrenal gland or kidney

slow postnatal weight gain ( J:76174 )

• by P3, homozygous mutant pups gain weight daily at a significantly lower rate than wild-type or heterozygous pups

• by P5, homozygous mutant pups weigh on average 30-40% less than control littermates

nervous system

decreased brain size ( J:76174 )

• at P8, homozygous mutant brains are proportionately smaller than those of heterozygous controls

decreased brain weight ( J:76174 )

• at P8, homozygous mutant brains weigh 30% less than those of heterozygous controls

abnormal cerebral cortex morphology ( J:76174 )

• at P8, mutant brains display notable inward depressions in both hemispheres of the cortical mantel, extending from the somatosensory cortex to the parietal associated cortex, auditory cortex and visual cortex

• a 1.75- and 1.4-fold increase in neuronal density is observed in cortical layer V and II, respectively, relative to controls; however, the thickness of cortical layer I, which contains axons from pyramidal neurons, is normal

• within cortical layer V, mutant cell bodies appear shrunken and show a 37% decrease in cross sectional area relative to controls

thin cerebral cortex ( J:76174 )

• at P8, homozygotes display a drastic atrophy of the brain cortical mantel as a result of postnatal malnutrition

• at P8, mutant brains show a 34.3% reduction in total cortical thickness from the white mater to pia

homeostasis/metabolism

decreased circulating leptin level ( J:76174 )

• at P8, malnourished homozygotes exhibit a ~7-fold reduction of serum leptin levels to the background detection range (2-3 ng/ml)

dehydration ( J:76174 )

• by P2, homozygotes appear unhealthy, dehydrated and malnourished

integument

dry skin ( J:76174 )

• by P2, mutant skin is dry

loose skin ( J:76174 )

• by P2, mutant skin forms loose folds around the body

pallor ( J:76174 )

• by P2, mutant skin is pale

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	Huntington's disease	DOID:12858	OMIM:143100	J:76174