Phenotypes associated with this allele

• Allele Symbol: Ehhadh^tm1Jkr
• Allele Name: targeted mutation 1, Janardan K Reddy
• Allele ID: MGI:1857810
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ehhadh^tm1Jkr/Ehhadh^tm1Jkr	involves: 129P2/OlaHsd * C57BL/6J	MGI:3606116
cx2	Ehhadh^tm1Jkr/Ehhadh^tm1Jkr Hsd17b4^tm1Baes/Hsd17b4^tm1Baes	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3606114

Genotype
MGI:3606116

hm1

• Allelic Composition: Ehhadh^tm1Jkr/Ehhadh^tm1Jkr
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

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

cellular

abnormal peroxisome physiology ( J:55395 )

• peroxisime proliferative response to cibrofibrate is blunted in the liver

homeostasis/metabolism

abnormal lipid homeostasis ( J:104835 )

• decreased oxidation of long chain fatty acids as well as decreased esterification

Genotype
MGI:3606114

cx2

• Allelic Composition: Ehhadh^tm1Jkr/Ehhadh^tm1Jkr; Hsd17b4^tm1Baes/Hsd17b4^tm1Baes
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J

Growth retardation and hypotonia in Ehhadh^tm1Jkr/Ehhadh^tm1Jkr Hsd17b4^tm1Baes/Hsd17b4^tm1Baes mice

mortality/aging

neonatal lethality, incomplete penetrance ( J:104835 )

• about one third of homozygotes die within 24 hours of birth

postnatal lethality, incomplete penetrance ( J:89945 )

• most died before weaning and the few surviving as much as 5 weeks were still suckling and not eating solid food

• some died in the first 3 days after birth with an inability to suckle

growth/size/body

postnatal growth retardation ( J:89945 , J:104835 )

• very striking growth retardation (J:89945)

• homozygotes are between 66 and 90% of normal weight (J:104835)

behavior/neurological

abnormal suckling behavior ( J:89945 )

• some show difficulty suckling and usually die within 3 days of birth

decreased locomotor activity ( J:104835 )

• reduced activity in mice that die the first day

homeostasis/metabolism

abnormal lipid homeostasis ( J:104835 )

• complete blockade of beta oxidation in liver peroxisomes

• about a 20% residual capacity to oxidize long chain fatty acids

abnormal lipid level ( J:89945 , J:104835 )

• 7 fold increase in C26/C22 ratio in serum (J:89945)

• 3-4 fold increase in accumulation of long chain fatty acids in brain phospholipids (J:104835)

abnormal bile salt level ( J:99925 )

• altered bile salt concentration

decreased fatty acids level ( J:89945 )

• 3.5 fold decrease in docosahexaenoic acid in serum

liver/biliary system

microvesicular hepatic steatosis ( J:89945 )

• microvesicular fatty changes in the liver appear between 3 and 5 weeks of age

cellular

abnormal mitochondrial morphology ( J:89945 )

abnormal peroxisome morphology ( J:89945 )

• reduction in numbers of peroxisomes

nervous system

nervous system phenotype ( J:104835 )

N • no abnormalities are observed in cortical neuronal migration

muscle

hypotonia ( J:104835 )

• mice that die the first day suffer from severe hypotonia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
D-bifunctional protein deficiency		DOID:0090031	OMIM:261515	J:89945 , J:99925