Mouse Genome Informatics
hm1
    Acetm1Keb/Acetm1Keb
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• blood pressure is unaffected by angiotensin I infusion unlike in wild-type mice

cardiovascular system
• blood pressure is unaffected by angiotensin I infusion unlike in wild-type mice


Mouse Genome Informatics
hm2
    Acetm1Keb/Acetm1Keb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• contrary to previous findings (J:25284), homozygotes generated from F1 intercrosses are obtained at the expected Mendelian frequency (J:33018)

cardiovascular system
• homozygotes exhibit thickened intrarenal arteries and arterioles as a result of medial hyperplasia
• thickened and hyperplastic renal arteries are observed
• inflammatory cells can be seen around the renal arteries with some infiltration into the vessel wall
• homozygotes exhibit an increase in average pulse rates (676 12 beats/min) relative to wild-type (626 16 beats/min) or heterozygous mutant mice (625 8 beats/min)
• homozygotes exhibit a significantly reduced average systolic blood pressure (73.3 1.7 mm Hg) relative to wild-type (110.1 1.9 mm Hg) or heterozygous mutant mice (107.3 1.6 mm Hg)

renal/urinary system
• homozygotes exhibit thickened intrarenal arteries and arterioles as a result of medial hyperplasia
• thickened and hyperplastic renal arteries are observed
• inflammatory cells can be seen around the renal arteries with some infiltration into the vessel wall
• following water deprivation, homozygotes display a reduction in electrolyte concentration, with a significantly lower urinary sodium to potassium ratio
• following water deprivation, homozygotes produce ~50% of the total aldosterone levels found in the urine of wild-type mice
• following water deprivation, homozygotes exhibit increased potassium excretion relative to wild-type mice
• when water is freely accessible, homozygotes exhibit a slightly lower average urine osmolarity (770 30 mOSM/kg ) relative to wild-type mice (1070 60 mOSM/kg)
• following water deprivation, homozygotes produce a higher (2x) volume of urine that is <50% as concentrated (1300 10 mOSM/kg) than that of wild-type mice (3000 300 mOSM/kg)
• regions of inflammatory infiltrate are seen at the cortical medullary junction
• regions of inflammatory infiltrate are seen at the cortical medullary junction
• mutant kidneys display papillary atresia
• mutant kidneys display renal papillary atrophy
• mutant kidneys display a thinned medulla
• mutant kidneys display dilated renal calyses
• homozygotes display dilation of the renal pelvis and calyces
• homozygous mutant kidneys are ~75% of the mass of wild-type kidneys
• when water is freely accessible, homozygotes show a 2-fold increase in urinary output relative to wild-type mice

reproductive system
• male homozygotes sire significantly smaller litters than wild-type males (3.3 1.4 vs 9.7 1.5 pups per litter, respectively)
• male homozygotes display reduced fertility, despite normal testis histology and normal sperm number, morphology, and motility (J:33018)
• in contrast, female homozygotes are fertile and produce normal litter sizes (J:33018)

homeostasis/metabolism
• homozygotes display significantly increased plasma creatinine levels (0.56 0.06 mg/dl) relative to wild-type mice (0.30 0.04 mg/dl)
• following water deprivation, homozygotes display a reduction in electrolyte concentration, with a significantly lower urinary sodium to potassium ratio
• following water deprivation, homozygotes produce ~50% of the total aldosterone levels found in the urine of wild-type mice
• following water deprivation, homozygotes exhibit increased potassium excretion relative to wild-type mice
• when water is freely accessible, homozygotes exhibit a slightly lower average urine osmolarity (770 30 mOSM/kg ) relative to wild-type mice (1070 60 mOSM/kg)
• following water deprivation, homozygotes produce a higher (2x) volume of urine that is <50% as concentrated (1300 10 mOSM/kg) than that of wild-type mice (3000 300 mOSM/kg)

immune system
• regions of inflammatory infiltrate are seen at the cortical medullary junction


Mouse Genome Informatics
ht3
    Acetm1Keb/Ace+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
N
• unexpectedly, heterozygous males display no significant differences in systolic blood pressure (110.2 2.4 mm Hg) relative to wild-type males (109.9 2.3 mm Hg) (J:33018)


Mouse Genome Informatics
ht4
    Acetm1Keb/Acetm5Keb
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• plasma renin levels are elevated although less than in mice homozygous for Acetm1Keb
• conversion of angiotensin I into angiotensin II is reduced compared to wildtype mice and mice homozygous for Acetm5Keb