Phenotypes Associated with This Genotype

Genotype
MGI:6343393

• Allelic Composition: Ugt1^tm1.1Afmu/Ugt1^tm1.1Afmu
• Genetic Background: FVB.Cg-Ugt1^tm1.1Afmu

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

mortality/aging

postnatal lethality, complete penetrance ( J:216224 )

• Background Sensitivity: 50% survival at P11 on the congenic FVB/NJ background, longer than on the congenic C57BL/6J background

• Background Sensitivity: life-long phototherapy (exposure to blue light) treatment starting at P0 results in survival of all mice on the congenic FVB/N background compared to mice on the congenic C57BL/6J background which die within 20 days after birth

• about 27% of mice receiving phototherapy beginning at P8 to P20 survive whereas only 7% of mice treated from P0 to P8 with phototherapy survive

homeostasis/metabolism

increased circulating bilirubin level ( J:216224 )

• mice develop hyperbilirubinemia within 36 hours after birth

• Background Sensitivity: plasma total bilirubin levels are lower on the congenic FVB/N background than on the congenic C57BL/6J background

• Background Sensitivity: total plasma bilirubin of mice on the congenic FVB/NJ background increase with time, reaching levels of mice on the congenic C57BL/6J background at later time points

• phototherapy treatment from birth rescues all features of bilirubin neurotoxicity

• discontinuation of phototherapy treatment results in a rapid increase of bilirubin levels

liver/biliary system

jaundice ( J:216224 )

• mice are jaundiced as early as 36 hours after birth

nervous system

seizures ( J:216224 )

• mice exhibit seizures prior to death

abnormal cerebellum morphology ( J:216224 )

• increase in TUNEL+ cells in the cerebellum, in the external germinal layer, Purkinje cell layer, and the internal granular layer

• phototherapy treatment for 8 days after birth prevents major cerebellar abnormalities and continuous phototherapy treatment for 15 days from P0 to P15 prevents all morphological and functional deficits such as cerebellar alterations, differences in layer thickness, in the number and arborization of Purkinje cells and motor impairments

• survivors from P8-P20 phototherapy treatment show cerebellar hypoplasia, with the molecular layer and inner granule layer thickness reduced 73% and 54%, respectively, compared to wild-type mice at P15

• 10 days after discontinuation of phototherapy treatment at P20, mice show reduced molecular layer and inner granule layer thickness by 32% and 24%, respectively

thin external granule cell layer ( J:216224 )

• decrease in thickness of the external germinal layer

abnormal cerebellar Purkinje cell layer ( J:216224 )

• decrease in thickness of the Purkinje cell layer

abnormal Purkinje cell dendrite morphology ( J:216224 )

• mice exhibit a reduction in Purkinje cell dendritic arbor

• the Purkinje cell dendritic arbor is still impaired in phototherapy treated mice, with total length of the dendritic arbor and number of branching points from P0-P8 phototherapy treated mice reduced 16% and 17%, respectively compared to wild-type mice and mice have reduced dendritic complexity, however the average length of each branch is not reduced

• Purkinje cell dendrites from P0-P8 phototherapy treated mice have about 16% fewer spines/um

• 10 days after discontinuation of phototherapy treatment at P20, Purkinje cells show slightly improved dendritic arbor compared to treated mice at P15

decreased Purkinje cell number ( J:216224 )

• after receiving 7 days of phototherapy, mice show a 62% decrease in Purkinje cell number, suggesting that the high plasma bilirubin levels from P0 to P8 trigger substantial cell death that is not prevented by the successive phototherapy treatment

• 10 days after discontinuation of phototherapy treatment at P20, the number of Purkinje cells is decreased, with 52% less than in wild-type mice

• Background Sensitivity: however, mice on the congenic FVB/NJ background do not show a decrease in Purkinje cell density in the cerebella at P8 compared to mice on the congenic C57BL/6J background that show a reduction in Purkinje cell number

abnormal cerebellum fissure morphology ( J:216224 )

• cerebella shows modifications of the architecture of the cerebellar fissures

encephalopathy ( J:216224 )

• prior to death, mice show features of bilirubin encephalopathy such as lethargy, dystonia, and seizures

muscle

dystonia ( J:216224 )

• mice exhibit dystonia prior to death

behavior/neurological

lethargy ( J:216224 )

• mice exhibit lethargy prior to death

dystonia ( J:216224 )

• mice exhibit dystonia prior to death

impaired coordination ( J:216224 )

• survivors from P8-P20 phototherapy treatment are severely impaired in motor coordination on the rotarod at 1 and 2 months of age

• however, continuous phototherapy treatment for 15 days from P0 to P15 prevents motor impairments

seizures ( J:216224 )

• mice exhibit seizures prior to death

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neonatal jaundice		DOID:2383		J:216224