All Phenotypes Slc13a1<tm1Mark> MGI Mouse

• homozygotes show normal birth weights but are generally smaller than wild-type and heterozygous mice at 1 week of age

• however, significant differences are not apparent until 2 weeks after birth

• at 2 weeks of age, homozygotes of both sexes show a ~25% reduction in average body weight relative to wild-type or heterozygous counterparts

• weight disparity persists at least until 6 months of age

postnatal growth retardation ( J:86561 )

• homozygotes exhibit growth retardation associated with reduced IGFI serum levels

• growth retardation is evident between 2-6 weeks of age and is not compensated in adulthood

increased liver weight ( J:86561 )

• at 4 weeks of age, homozygotes show a small but significant increase in liver:body weight ratio (5.31 0.47%, n = 14) relative to heterozygous (4.67 0.50%, n = 18) and wild-type (4.57 0.22%, n = 9) littermates

decreased circulating insulin-like growth factor I level ( J:86561 )

• homozygotes show a >30% reduction in serum IGFI levels relative to wild-type mice

hyposulfatemia ( J:86561 )

• at all ages examined, homozygotes display a >75% reduction of serum sulfate concentrations relative to wild-type littermates

increased bile salt level ( J:86561 )

• homozygotes show a ~2- to 4-fold increase in serum levels of cholic, hyodeoxycholic, murocholic, chenocholic, glycoursodeoxycholic, glycolithocholic, and taurocholic acid relative to wild-type mice

increased urine sulfate level ( J:86561 )

• homozygotes display a higher urine SO₄^2-:creatinine ratio and a a 5-fold increase in fractional excretion index (FEI) for SO₄^2- relative to wild-type mice, while serum creatinine levels remain constant

• in contrast, homeostasis of other ions (including PO₄^2-, Ca²⁺, Na⁺, K⁺, and Cl^-) is normal, and no increase in urinary protein excretion is observed

abnormal enzyme/coenzyme activity ( J:86561 )

• homozygotes display a 1.5- to 2.0-fold increase in the level of liver phenol sulfotransferase (ST) activity relative to wild-type littermates

• however, the average ST activity is not significantly elevated (1.1-fold increase) relative to heterozygous mice

increased urine sulfate level ( J:86561 )

• homozygotes display a higher urine SO₄^2-:creatinine ratio and a a 5-fold increase in fractional excretion index (FEI) for SO₄^2- relative to wild-type mice, while serum creatinine levels remain constant

• in contrast, homeostasis of other ions (including PO₄^2-, Ca²⁺, Na⁺, K⁺, and Cl^-) is normal, and no increase in urinary protein excretion is observed

abnormal renal reabsorption ( J:86561 )

• in homozygotes, Na⁺-dependent SO₄^2- uptake is reduced by 90% in renal brush-border membrane vesicles (BBMVs) and abolished in ileal BBMVs

• in contrast, Na⁺-independent SO₄^2- uptake and Na⁺-dependent glucose uptake remain unaffected relative to wild-type controls

increased miscarriage rate ( J:86561 )

• a few female homozygotes display blood spotting or miscarriages in several pregnancies at ~14 days of gestation

reduced female fertility ( J:86561 )

• female, but not male, homozygotes exhibit reduced fertility relative to wild-type or heterozygous females

decreased litter size ( J:86561 )

• female homozygotes display a 60% reduction in litter size relative to wild-type or heterozygous littermates

clonic seizures ( J:86561 )

• at ~8 months of age, 27% of homozygotes exhibit spontaneous clonic seizures

• in some homozygotes, seizures can be elicited by the stress of simple handling

• affected homozygotes usually recover within 2 min

short femur ( J:86561 )

• at 4 weeks of age, homozygotes display reduced femoral length (0.91 0.04 cm) relative to wild-type littermates (1.03 0.03 cm)

short tail ( J:86561 )

• starting at 3 weeks of age, homozygotes show a ~10% reduction in tail length relative to wild-type and heterozygous littermates