Phenotypes associated with this allele

• Allele Symbol: Slc6a18^tm1Mca
• Allele Name: targeted mutation 1, Marc G Caron
• Allele ID: MGI:3043846
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Slc6a18^tm1Mca/Slc6a18^tm1Mca	involves: 129X1/SvJ * C57BL/6J	MGI:3043848

Genotype
MGI:3043848

hm1

• Allelic Composition: Slc6a18^tm1Mca/Slc6a18^tm1Mca
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

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

renal/urinary system

hyperglycinuria ( J:89891 )

• homozygotes exhibit a significant increase in urinary glycine levels, with a ~4-fold rise in the urinary glycine/creatinine ratio relative to wild-type control mice

• however, plasma glycine levels remain unaffected, and the urinary and plasma content of other amino acids (including Ala, Val, Pro1, Leu/Ile, Met, Phe, Tyr, Asp, and Glu) are all within normal range

abnormal renal reabsorption ( J:89891 )

• adult homozygotes display a deficiency of renal glycine reabsorption (~75% of wild-type levels), as revealed by tandem mass spectrometry

• in vivo tracing of renal glycine reabsorption indicates that, unlike wild-type mice, homozygotes show absence of [¹⁴C]glycine accumulation in the outer medulla, as determined by autoradiography

abnormal renal transport ( J:89891 )

• apical membrane-enriched brush border membrane vesicles (BBMVs) isolated from the kidney cortex of homozygous mutant mice show a dramatic reduction in [³H] glycine uptake activity at substrate concentrations less than 1 mM

• close analysis of the uptake kinetics by the Eadie-Hofstee method shows that the high-affinity component of renal glycine reabsorption is absent in mutant mice

• in contrast, uptake of leucine and methionine by mutant renal BBMVs is within wild-type values at all substrate concentrations used

cardiovascular system

hypertension ( J:89891 )

• homozygotes exhibit a mild hypertension relative to wild-type mice

increased systemic arterial systolic blood pressure ( J:89891 )

• conscious homozygotes display a significantly increased systolic blood pressure relative to wild-type control mice (127 3 versus 114 2 mmHg, respectively)

• increase in mean systolic blood pressure is observed on both a low-salt (<0.04% NaCl) and a high-salt (6% NaCl) diet

• supplementation with 0.1 g of glycine/ml in drinking water reduces the systolic blood pressure of mutant mice to virtually wild-type levels, causing it to fall from 127 3 to 115 3 mmHg, but has little effect on the blood pressure of wild-type mice

homeostasis/metabolism

hyperglycinuria ( J:89891 )

• homozygotes exhibit a significant increase in urinary glycine levels, with a ~4-fold rise in the urinary glycine/creatinine ratio relative to wild-type control mice

• however, plasma glycine levels remain unaffected, and the urinary and plasma content of other amino acids (including Ala, Val, Pro1, Leu/Ile, Met, Phe, Tyr, Asp, and Glu) are all within normal range