Mouse Genome Informatics
hm
    Slc4a1tm1Llp/Slc4a1tm1Llp
involves: 129S4/SvJae * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• oral acid loading for more than 24 hours resulted in death from apparent dehydration and massive hemolysis
• 85% of animals die within two weeks of birth
• about 16% survival at 10 to 14 weeks of age from crosses of homozygous males to heterozygous females

renal/urinary system
• hypocitraturia is seen at 12 weeks of age
• seen at 12 weeks of age
• alkaline urine with reduced excretion of net acid and titratable acids
• reduction in inner medullary mass resembling that in chronic hydronephrosis
• inner medullary atrophy with a compensatory increase in abundance of outer medullary AQP2
• nephrocalcinosis indicted by predominantly medullary calcium phosphate deposits
• however, formation of calculi (nephrolithiasis) is not detected
• modest decrease in acidification rate of cultured type A intercalated cells following chloride readdition to a chloride free bath
• acidification of cultured type A intercalated cells is insensitive to diBA(5)C4 and shows reduced sensitivity to 4-4'-diisothiocyanatostilbene-2,2'-disulfonic acid suggesting upregulation of pharmacologically distinct anion exchange activity
• oral acid loading results in decreased creatinine clearance probably reflecting systemic dehydration
• 24 hour urine output is increased 2 to 4 fold compared to controls

homeostasis/metabolism
• increase in serum osmolarity is seen at 12 weeks of age suggesting mild systemic dehydration
• oral acid loading greatly increases plasma osmolarity without altering urinary osmolality
• low blood pH seen at 12 weeks of age
• seen at 12 weeks of age
• low blood bicarbonate levels seen at 12 weeks of age
• slight increase at 12 weeks of age
• oral acid loading induces systemic dehydration
• slight increase at 12 weeks of age
• severe metabolic acidosis with low blood pH and bicarbonate levels is seen in 12 week old mice
• challenge with oral acid loading disproportionately worsens metabolic acidosis compared to similarly treated wild-type or heterozygous controls
• hypocitraturia is seen at 12 weeks of age
• seen at 12 weeks of age
• alkaline urine with reduced excretion of net acid and titratable acids
• oral acid loading for more than 24 hours resulted in death from apparent dehydration and massive hemolysis

hematopoietic system
• severely decreased in mice at 5 - 7 days and 14 weeks of age (J:148154)
• decreased hemoglobin content
• nucleated erythroid cells are found in circulation
• severe hemolytic anemia noted in animals surviving to adulthood
• incomplete penetrance; reticulocytes are seen in only 2 of 12 newborn mice tested
• presence of binucleated erythroblasts; 4% of mice compared to < 1% of wild-type mice
• greater than 70% reticulocytosis in mice at 5 - 7 days of age (J:148154)
• spleens are 15 times larger in homozygotes than in littermates
• oral acid loading induces severe hemolysis

growth/size
• oral acid loading results in loss of 14% of initial body weight within 24 hours
• noted in animals surviving to adulthood
• survivors grow more slowly

immune system
• spleens are 15 times larger in homozygotes than in littermates

integument
• pale appearace noted at birth

Mouse Models of Human Disease
OMIM IDRef(s)
Renal Tubular Acidosis, Distal, Autosomal Recessive; RTADR 602722 J:148154