Phenotypes associated with this allele

• Allele Symbol: Ugt1^tm1.1Afmu
• Allele Name: targeted mutation 1.1, Andres F Muro
• Allele ID: MGI:5320594
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ugt1^tm1.1Afmu/Ugt1^tm1.1Afmu	B6.Cg-Ugt1^tm1.1Afmu	MGI:6343389
hm2	Ugt1^tm1.1Afmu/Ugt1^tm1.1Afmu	FVB.Cg-Ugt1^tm1.1Afmu	MGI:6343393
hm3	Ugt1^tm1.1Afmu/Ugt1^tm1.1Afmu	involves: 129 * C57BL/6 * SJL	MGI:5320595

Genotype
MGI:6343389

hm1

• Allelic Composition: Ugt1^tm1.1Afmu/Ugt1^tm1.1Afmu
• Genetic Background: B6.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% mortality at P5 on the congenic C57BL/6J background, earlier than on the congenic FVB/NJ background

• Background Sensitivity: newborns treated with phototherapy (exposure to blue light) die within 20 days after birth on the congenic C57BL/6J background while mice on the congenic FVB/NJ background survive to adulthood

liver/biliary system

jaundice ( J:216224 )

• mice are jaundiced as early as 36 hours after birth

homeostasis/metabolism

increased circulating bilirubin level ( J:216224 )

• mice develop hyperbilirubinemia within 36 hours after birth

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

nervous system

decreased Purkinje cell number ( J:216224 )

• Background Sensitivity: mice on the congenic C57BL/6 background show a 37% reduction in Purkinje cell number in the cerebella at P8 compared to no differences in Purkinje cell density on the congenic FVB/NJ background

Genotype
MGI:6343393

hm2

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

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

Genotype
MGI:5320595

hm3

• Allelic Composition: Ugt1^tm1.1Afmu/Ugt1^tm1.1Afmu
• Genetic Background: involves: 129 * C57BL/6 * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:182805 )

• by P11

• mice given phototherapy at P2 show prolonged survival although none survived past P20

behavior/neurological

abnormal suckling behavior ( J:182805 )

• deceased feeding

abnormal motor capabilities/coordination/movement ( J:182805 )

• severe motor impairment detectable by P3

• stimulus-evoked hyperactivity resembling seizures is detected at P7 - P11

athetotic walking movements ( J:182805 )

• at P7 - P11

dystonia ( J:182805 )

• at P7 - P11

ataxia ( J:182805 )

• at P7 - P11

abnormal limb posture ( J:182805 )

• of the rear limbs

abnormal locomotor activation ( J:182805 )

• poor and slow movement

nervous system

increased neuron apoptosis ( J:182805 )

• in the cerebellum at P5

abnormal cerebellum morphology ( J:182805 )

• less well developed at P5

thin external granule cell layer ( J:182805 )

• at P5

abnormal cerebellar layer morphology ( J:182805 )

• abnormal stratification at P5

abnormal cerebellar Purkinje cell layer ( J:182805 )

• very disorganized at P5

abnormal Purkinje cell dendrite morphology ( J:182805 )

• underdeveloped dendritic arbor at P5

decreased Purkinje cell number ( J:182805 )

abnormal cerebellar granule layer morphology ( J:182805 )

• increased depth at P5

abnormal cerebellum fissure morphology ( J:182805 )

• misshapen at P5

• fissures in lobules I, IV, VIa, and IXb are almost absent at P5

homeostasis/metabolism

increased circulating bilirubin level ( J:182805 )

• unconjugated bilirubin levels reach about 42 times higher than controls by P5

• mice given phototherapy at P2 show lower levels of bilirubin

liver/biliary system

abnormal gallbladder morphology ( J:182805 )

• colorless rather than yellowish reflecting the absence of glucuronidated bilirubin

jaundice ( J:182805 )

• develops as early as 36 h after birth

muscle

dystonia ( J:182805 )

• at P7 - P11

cellular

increased neuron apoptosis ( J:182805 )

• in the cerebellum at P5

endocrine/exocrine glands

abnormal gallbladder morphology ( J:182805 )

• colorless rather than yellowish reflecting the absence of glucuronidated bilirubin

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Crigler-Najjar syndrome		DOID:3803	OMIM:218800	J:182805