Phenotypes Associated with This Genotype

Genotype
MGI:5805971

• Allelic Composition: Hoga1^{tm2a(KOMP)Wtsi}/Hoga1^{tm2a(KOMP)Wtsi}
• Genetic Background: involves: C57BL/6N
• Cell Lines: EPD0380_4_H08

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

homeostasis/metabolism

abnormal blood homeostasis ( J:231386 , J:231386 )

• on a Hyp-free diet (devoid of trans-4-hydroxy-L-proline), homozygotes of both sexes exhibit significantly higher plasma 2,4-dihydroxyglutarate (DHG) levels than wild-type controls (J:231386)

• on a Hyp-free diet, female homozygotes show higher plasma glycolate levels than male homozygotes (J:231386)

• on a 1% Hyp diet, homozygotes of both sexes show significantly higher plasma 4-hydroxy-2-oxoglutarate (HOG) and DHG levels than wild-type controls (J:231386)

♀ • on a 1% Hyp diet, female homozygotes show a ~2-fold decrease in plasma glycolate levels relative to wild-type females (J:231386)

abnormal urine homeostasis ( J:231386 , J:231386 , J:231386 )

• on a Hyp-free diet, homozygotes of both sexes exhibit significantly higher urine DHG levels than wild-type controls (8-fold and 7-fold increase in males and females, respectively) (J:231386)

• on a 1% Hyp diet, homozygotes of both sexes show significantly higher urine HOG and DHG levels than wild-type controls (J:231386)

• homozygotes fed either a Hyp-free diet or a 1% Hyp diet do NOT exhibit hyperoxaluria relative to similarly treated wild-type controls (J:231386)

• following infusion with low levels of ¹³C₅-¹⁵N-Hyp, homozygotes display normal urinary ¹³C₂-oxalate and ¹³C₂-glycolate excretions, with a similar contribution of Hyp metabolism to urinary oxalate excretion relative to wild-type controls (J:231386)

♀ • on a 1% Hyp diet, female homozygotes show a lower increase in urine glycolate levels than wild-type females (~6-fold vs ~14-fold, respectively) (J:231386)

♂ • on a Hyp-free diet, male homozygotes show a lower fractional clearance of glycolate than wild-type males (J:231386)

♂ • following infusion with low levels of ¹³C₅-¹⁵N-Hyp, urine ¹³C₅-DHG levels are increased in male homozygotes but remain undetectable in wild-type controls, indicating that the DHG detected in wild-type mice on a Hyp-free diet is not derived from Hyp metabolism (J:231386)

liver/biliary system

abnormal liver physiology ( J:231386 , J:231386 )

• on a 1% Hyp diet, homozygotes of both sexes show significantly higher DHG levels in liver tissue than wild-type controls (J:231386)

♀ • on a 1% Hyp diet, female homozygotes show significantly increased HOG levels in liver tissue relative to male homozygotes or wild-type controls of both sexes (J:231386)

renal/urinary system

abnormal urine homeostasis ( J:231386 , J:231386 , J:231386 )

• on a Hyp-free diet, homozygotes of both sexes exhibit significantly higher urine DHG levels than wild-type controls (8-fold and 7-fold increase in males and females, respectively) (J:231386)

• on a 1% Hyp diet, homozygotes of both sexes show significantly higher urine HOG and DHG levels than wild-type controls (J:231386)

• homozygotes fed either a Hyp-free diet or a 1% Hyp diet do NOT exhibit hyperoxaluria relative to similarly treated wild-type controls (J:231386)

• following infusion with low levels of ¹³C₅-¹⁵N-Hyp, homozygotes display normal urinary ¹³C₂-oxalate and ¹³C₂-glycolate excretions, with a similar contribution of Hyp metabolism to urinary oxalate excretion relative to wild-type controls (J:231386)

♀ • on a 1% Hyp diet, female homozygotes show a lower increase in urine glycolate levels than wild-type females (~6-fold vs ~14-fold, respectively) (J:231386)

♂ • on a Hyp-free diet, male homozygotes show a lower fractional clearance of glycolate than wild-type males (J:231386)

♂ • following infusion with low levels of ¹³C₅-¹⁵N-Hyp, urine ¹³C₅-DHG levels are increased in male homozygotes but remain undetectable in wild-type controls, indicating that the DHG detected in wild-type mice on a Hyp-free diet is not derived from Hyp metabolism (J:231386)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
primary hyperoxaluria		DOID:2977	OMIM:PS259900	J:231386