Phenotypes associated with this allele

• Allele Symbol: Hacd2^{tm1a(EUCOMM)Hmgu}
• Allele Name: targeted mutation 1a, Helmholtz Zentrum Muenchen GmbH
• Allele ID: MGI:4841604
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hacd2^tm1a(EUCOMM)Hmgu/Hacd2^tm1a(EUCOMM)Hmgu	involves: C57BL/6N	MGI:7447072

Genotype
MGI:7447072

hm1

• Allelic Composition: Hacd2^{tm1a(EUCOMM)Hmgu}/Hacd2^{tm1a(EUCOMM)Hmgu}
• Genetic Background: involves: C57BL/6N

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

mortality/aging

postnatal lethality, complete penetrance ( J:333944 )

• mice fail to thrive and die within 1 to 4 weeks after birth; no survivors reach weaning age

growth/size/body

decreased body weight ( J:333944 )

• at P5, body mass is significantly reduced but pups are overtly indistinguishable from wild-type and heterozygous controls

cachexia ( J:333944 )

• pups become progressively more cachectic within 1 to 5 days after their growth arrest

postnatal growth retardation ( J:333944 )

• at a variable time point between P5 and P22, all pups exhibit a sudden growth arrest followed by fatal cachexia and lethargy, justifying euthanasia

• at the terminal stage (P19, humane endpoint), mice have a lower body mass resulting from a reduced mass of several organs, including the liver, BAT and muscle

behavior/neurological

lethargy ( J:333944 )

• pups become progressively more lethargic within 1 to 5 days after their growth arrest

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:333944 )

N • lipidomic analysis showed no alterations in fatty acid and phospholipid content in the liver, kidney and BAT, as well as no changes in mitochondrial cardiolipin composition in the liver, kidney and heart

hypoglycemia ( J:333944 )

• at P7, all asymptomatic, still growing pups show hypoglycemia

increased circulating lactate level ( J:333944 )

• at P7, all asymptomatic, still growing pups show a 2-fold increase in lactatemia in the context of a devastating systemic disorder

lactic acidosis ( J:333944 )

• fatal deterioration of pups is likely due to lactic acidosis

cellular

abnormal mitochondrial physiology ( J:333944 )

• pups exhibit severe mitochondrial dysfunction in the kidney and liver

abnormal oxidative phosphorylation ( J:333944 )

• at P9-P14, both the kidney and liver of asymptomatic, still growing pups show a marked decrease in the respiratory control ratio i.e., ratio of phosphorylating to non-phosphorylating oxidation rate (-46% and -54%, respectively)

• in brown adipose tissue (BAT), the respiratory control ratio is unchanged but phosphorylating and non-phosphorylating respiration are both significantly decreased

abnormal mitochondrial ATP synthesis coupled electron transport ( J:333944 )

• pups show a reduced mitochondrial coupling in the kidney and liver from early stages

• asymptomatic, still growing pups show a marked reduction of cytochrome c oxidase (COX) activity in kidney cortex sections; after growth arrest, both citrate synthase (CS) and COX activity tend to decline in kidney lysates along with mRNA expression of Ppargc1a (involved in mitochondrial biogenesis), suggesting absence of an adaptative response in the kidney

• conversely, COX activity tends to increase in liver lysates along with a parallel increase in mRNA expression of the Cs (citrate synthase) gene and genes involved in mitochondrial biogenesis (Ppargc1a, Nrf1, and Tfam), suggesting an adaptative response in the liver to cope with a reduced mitochondrial coupling efficiency

adipose tissue

abnormal brown adipose tissue thermogenesis ( J:333944 )

• at P7, pups show a significant reduction in BAT-related interscapular thermogenesis

• however, the internal temperature is preserved at P5-P9