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Phenotypes Associated with This Genotype
Genotype
MGI:3610388
Allelic
Composition
Hnf1atm1Mya/Hnf1atm1Mya
Genetic
Background
involves: 129S2/SvPas
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hnf1atm1Mya mutation (0 available); any Hnf1a mutation (7 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
N
• at birth, homozygotes are obtained at a slightly reduced frequency (20% vs expected 25%), suggesting embryonic/perinatal loss (J:31627)
• at birth, homozygotes are obtained at a slightly reduced frequency (20% vs expected 25%), suggesting embryonic/perinatal loss (J:31627)
• only 50% of homozygotes survive to P26, with viability sharply reduced at P25 (J:31627)
• less than 15% of homozygotes survive to P42, and less than 1% survive beyond 3 months (J:31627)
• only 50% of homozygotes survive to P26, with viability sharply reduced at P25 (J:31627)
• less than 15% of homozygotes survive to P42, and less than 1% survive beyond 3 months (J:31627)

liver/biliary system
• at ~P14, homozygotes show severe hepatomegaly (J:31627)
• at ~P14, homozygotes show severe hepatomegaly (J:31627)
• at ~P14, the mutant liver to body weight ratio reaches 10%, and is on average twice that of heterozygous and wild-type littermates (J:31627)
• at ~P14, the mutant liver to body weight ratio reaches 10%, and is on average twice that of heterozygous and wild-type littermates (J:31627)
• 20% of homozygotes with enlarged livers display steatosis (J:31627)
• 20% of homozygotes with enlarged livers display steatosis (J:31627)
• homozygotes exhibit increased cholesterol, transaminase, and bilirubin levels, suggesting hepatocellular damage and liver dysfunction (J:31627)
• homozygotes exhibit increased cholesterol, transaminase, and bilirubin levels, suggesting hepatocellular damage and liver dysfunction (J:31627)
• newborn homozygotes appear slightly yellowish relative to wild-type pups (J:31627)
• newborn homozygotes appear slightly yellowish relative to wild-type pups (J:31627)

homeostasis/metabolism
• weaned homozygotes exhibit very high hydroxyproline levels, and suffer from severe hyperphenylalaninemia (9- to 70-fold increase) caused by lack of transcription of the phenylalanine hydroxylase gene (J:31627)
• in contrast, levels of arginine, uric acid, and lysine are significantly reduced, while postprandial glycemia remains unaffected (J:31627)
• surprisingly, albumin and total plasma protein content is comparable to that of wild-type littermates (J:31627)
• weaned homozygotes exhibit very high hydroxyproline levels, and suffer from severe hyperphenylalaninemia (9- to 70-fold increase) caused by lack of transcription of the phenylalanine hydroxylase gene (J:31627)
• in contrast, levels of arginine, uric acid, and lysine are significantly reduced, while postprandial glycemia remains unaffected (J:31627)
• surprisingly, albumin and total plasma protein content is comparable to that of wild-type littermates (J:31627)
• homozygotes exhibit a mild hyperammonemia (1.5- to 2-fold increase), that is often associated with orotic aciduria (J:31627)
• homozygotes exhibit a mild hyperammonemia (1.5- to 2-fold increase), that is often associated with orotic aciduria (J:31627)
• homozygotes exhibit a mild (3- to 10-fold) increase in plasma bilirubin levels (J:31627)
• homozygotes exhibit a mild (3- to 10-fold) increase in plasma bilirubin levels (J:31627)
• homozygotes probably attempt to compensate for their massive urinary glucose loss with constitutively active gluconeogenesis and polyphagia (J:31627)
• defective glucose/energy balance eventually leads to protein catabolism and wasting (J:31627)
• homozygotes probably attempt to compensate for their massive urinary glucose loss with constitutively active gluconeogenesis and polyphagia (J:31627)
• defective glucose/energy balance eventually leads to protein catabolism and wasting (J:31627)
• homozygotes exhibit increased renal leakage in the proximal tubule reabsorption process, with glucose leaking 878 times more than in wild-type littermates (J:31627)
• Scatchard plot analysis of phlorizin binding to brush border vesicles indicates a 2-fold reduction in the number Na+/glucose cotransporter molecules (J:31627)
• homozygotes exhibit increased renal leakage in the proximal tubule reabsorption process, with glucose leaking 878 times more than in wild-type littermates (J:31627)
• Scatchard plot analysis of phlorizin binding to brush border vesicles indicates a 2-fold reduction in the number Na+/glucose cotransporter molecules (J:31627)
• homozygotes exhibit increased renal leakage in the proximal tubule reabsorption process, resulting in loss of arginine (65% loss vs 0.4% in wild-type) and other amino acids and metabolites (e.g. citrulline, hydroxyproline, uric acid) in the urine (J:31627)
• homozygotes exhibit increased renal leakage in the proximal tubule reabsorption process, resulting in loss of arginine (65% loss vs 0.4% in wild-type) and other amino acids and metabolites (e.g. citrulline, hydroxyproline, uric acid) in the urine (J:31627)
• as early as P2-P5, normoglycemic homozygous pups exhibit very high urine glucose concentrations (240-1400 mM), with an average daily glucose loss of 600 mg (J:31627)
• as early as P2-P5, normoglycemic homozygous pups exhibit very high urine glucose concentrations (240-1400 mM), with an average daily glucose loss of 600 mg (J:31627)
• homozygotes exhibit an ~6-fold increase in urinary calcium/creatine ratio relative to wild-type mice (J:31627)
• homozygotes exhibit an ~6-fold increase in urinary calcium/creatine ratio relative to wild-type mice (J:31627)
• mild hyperammonemia is often associated with orotic aciduria (J:31627)
• mild hyperammonemia is often associated with orotic aciduria (J:31627)

renal/urinary system
• homozygotes exhibit increased renal leakage in the proximal tubule reabsorption process, with glucose leaking 878 times more than in wild-type littermates (J:31627)
• Scatchard plot analysis of phlorizin binding to brush border vesicles indicates a 2-fold reduction in the number Na+/glucose cotransporter molecules (J:31627)
• homozygotes exhibit increased renal leakage in the proximal tubule reabsorption process, with glucose leaking 878 times more than in wild-type littermates (J:31627)
• Scatchard plot analysis of phlorizin binding to brush border vesicles indicates a 2-fold reduction in the number Na+/glucose cotransporter molecules (J:31627)
• homozygotes exhibit increased renal leakage in the proximal tubule reabsorption process, resulting in loss of arginine (65% loss vs 0.4% in wild-type) and other amino acids and metabolites (e.g. citrulline, hydroxyproline, uric acid) in the urine (J:31627)
• homozygotes exhibit increased renal leakage in the proximal tubule reabsorption process, resulting in loss of arginine (65% loss vs 0.4% in wild-type) and other amino acids and metabolites (e.g. citrulline, hydroxyproline, uric acid) in the urine (J:31627)
• as early as P2-P5, normoglycemic homozygous pups exhibit very high urine glucose concentrations (240-1400 mM), with an average daily glucose loss of 600 mg (J:31627)
• as early as P2-P5, normoglycemic homozygous pups exhibit very high urine glucose concentrations (240-1400 mM), with an average daily glucose loss of 600 mg (J:31627)
• homozygotes exhibit an ~6-fold increase in urinary calcium/creatine ratio relative to wild-type mice (J:31627)
• homozygotes exhibit an ~6-fold increase in urinary calcium/creatine ratio relative to wild-type mice (J:31627)
• mild hyperammonemia is often associated with orotic aciduria (J:31627)
• mild hyperammonemia is often associated with orotic aciduria (J:31627)
• homozygotes show an ~3-fold reduction in the glomerular filtration rate, as calculated on the basis of renal creatinine clearance normalized per body weight (J:31627)
• homozygotes show an ~3-fold reduction in the glomerular filtration rate, as calculated on the basis of renal creatinine clearance normalized per body weight (J:31627)
• in homozygotes, diuresis is 2.6-15 times higher and in some cases reaches 85% of body weight in 24 hrs (J:31627)
• 50% of homozygotes show a daily diuresis of >40% of their body weight (J:31627)
• as expected, polyuria shows a positive and significant correlation with urinary glucose loss (J:31627)
• in homozygotes, diuresis is 2.6-15 times higher and in some cases reaches 85% of body weight in 24 hrs (J:31627)
• 50% of homozygotes show a daily diuresis of >40% of their body weight (J:31627)
• as expected, polyuria shows a positive and significant correlation with urinary glucose loss (J:31627)

growth/size/body
• after weaning, the body weight of mutant mice is 40%-80% that of wild-type littermates (J:31627)
• after weaning, the body weight of mutant mice is 40%-80% that of wild-type littermates (J:31627)
• homozygotes start exhibiting progressive wasting and cachexia at the end of the second postnatal week (J:31627)
• homozygotes start exhibiting progressive wasting and cachexia at the end of the second postnatal week (J:31627)
• homozygotes exhibit growth retardation after the first postnatal week (P7) (J:31627)
• homozygotes exhibit growth retardation after the first postnatal week (P7) (J:31627)

behavior/neurological
• the few surviving weaned homozygotes are polyphagic, with a 30% increase in food intake per body weight unit (J:31627)
• weaned homozygotes cannot tolerate overnight fasting, become weak and die the next morning (J:31627)
• the few surviving weaned homozygotes are polyphagic, with a 30% increase in food intake per body weight unit (J:31627)
• weaned homozygotes cannot tolerate overnight fasting, become weak and die the next morning (J:31627)

muscle
• by P20, homozygotes display muscular atrophy (J:31627)
• by P20, homozygotes display muscular atrophy (J:31627)

digestive/alimentary system
• 20% of weaned homozygotes show a disorganized, looser gastric glandular epithelium of reduced thickness (J:31627)
• 20% of weaned homozygotes show a disorganized, looser gastric glandular epithelium of reduced thickness (J:31627)

skeleton
• by P20, homozygotes exhibit extensive bone demineralization (J:31627)
• by P20, homozygotes exhibit extensive bone demineralization (J:31627)

adipose tissue
• by P20, homozygotes show loss of subcutaneous fat (J:31627)
• by P20, homozygotes show loss of subcutaneous fat (J:31627)

integument
• by P20, homozygotes show loss of subcutaneous fat (J:31627)
• by P20, homozygotes show loss of subcutaneous fat (J:31627)

cellular

Mouse Models of Human Disease
OMIM ID Ref(s)
Phenylketonuria; PKU 261600 J:31627


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
02/02/2016
MGI 6.02
The Jackson Laboratory