mortality/aging
• increase in mortality 24 h after infection with S. pneumoniae strain type 3
|
immune system
• S. pneumoniae strain type 3 induced increases in intracranial pressure and cerebral spinal fluid leukocyte counts and impairment of the brain blood barrier are enhanced
• display more pronounced subarachnoid and ventricular granulocytic infiltrates 24 h after infection with S. pneumoniae strain type 3
|
• increase in mortality 24 h after infection with S. pneumoniae strain type 3
|
cardiovascular system
• mice raised in mild hypoxia display a decreased vessel volume density compared to similarly raised wild-type controls
|
• left ventricular chamber size is reduced
|
• age related
|
• sarcomere shortening in response to a beta3-adrenergic agonist is absent
|
• increase in the beta-adrenergic inotropic responses
|
• mild
|
• Ca2+ transients in response to a beta3-adrenergic agonist are absent
|
• in male, but not female, mice
(J:108540)
|
• arterial elastance is increased
(J:75645)
• relaxation of mesenteric arteries and the aorta of acetylcholine-treat male mice is inhibited unlike similarly treated female and wild-type mice
(J:108540)
|
• following exposure to 75% oxygen from P7 to P12, extraretinal neovascularization upon return to room air is significantly decreased compared to similarly treated wild-type mice
|
• neointimal formation after cuff injury is increased compared to wild-type controls
(J:119617)
• neointimal formation after cuff injury is increased in males relative to females
(J:119617)
• neointimal formation after cuff injury is decreased in pregnant females compared to non pregnant females; however, the level in mutants is still increased compared to wild-type
(J:119617)
• at day 28 following femoral artery resection limb perfusion remains impaired unlike in wild-type mice
(J:139343)
• capillary density remains reduced for a longer period of time following femoral artery resection
(J:139343)
• VEGF treatment fails to improve angiogenesis following femoral artery resection
(J:139343)
|
homeostasis/metabolism
N |
• despite increase in visceral fat, no change in triacylglycerol levels in the blood are detected
|
• neointimal formation after cuff injury is increased compared to wild-type controls
(J:119617)
• neointimal formation after cuff injury is increased in males relative to females
(J:119617)
• neointimal formation after cuff injury is decreased in pregnant females compared to non pregnant females; however, the level in mutants is still increased compared to wild-type
(J:119617)
• at day 28 following femoral artery resection limb perfusion remains impaired unlike in wild-type mice
(J:139343)
• capillary density remains reduced for a longer period of time following femoral artery resection
(J:139343)
• VEGF treatment fails to improve angiogenesis following femoral artery resection
(J:139343)
|
• following superovulation the plasma estradiol level is significantly higher in homozygous mutant females compared to wild-type mice
|
• relaxation of mesenteric arteries and the aorta of acetylcholine-treat male mice is inhibited unlike similarly treated female and wild-type mice
|
reproductive system
|
• oocytes with an unusually large first polar body are observed
|
|
• a variety of abnormal characteristics noted including enlarged first polar body, cytoplasmic cleavage, blebbing, premature release of the second polar body and cell division
|
|
• fewer oocytes from mutant females reach metaphase II of meiosis but instead remain in metaphase I or become abnormal with an enlarged first polar body, cytoplasmic cleavage, blebbing, and/or premature release of the second polar body
• many of the arrested and abnormal oocytes are also dying
|
small ovary
(
J:89702
)
|
• ovaries from homozygous mutant females are significantly smaller than those from wild-type females following stimulation by exogenous gonadotropins
|
|
• the number of ovarian rupture sites stimulated by exogenous gonadotropins is decreased in mutant females compared to wild-type mice
|
|
• the number of oocytes released following stimulation by exogenous gonadotropins is decreased in mutant females compared to wild-type mice
• mutants produced 62% fewer oocytes than controls after superovualtion
|
|
• oestrus cycle length and individual variability in cycle length is reduced in homozygous mutant females compared to C57BL/6J wild-type mice
|
• homozygous mutant females have a smaller average litter size compared to wild-type mice
(J:58361)
• a lower percentage of pups are weaned by homozygous mutant females compared to wild-type mice
(J:58361)
• matings between homozygous mutants produce smaller litters size compared to matings between wild-type mice or heterozygous mice
(J:89702)
• a lower percentage of pups born to homozygous mutant females survive to weaning
(J:89702)
• litters from homozygous mutant females have a decreased ratio of female to male pups
(J:89702)
|
endocrine/exocrine glands
small ovary
(
J:89702
)
|
• ovaries from homozygous mutant females are significantly smaller than those from wild-type females following stimulation by exogenous gonadotropins
|
muscle
• age related
|
• sarcomere shortening in response to a beta3-adrenergic agonist is absent
|
• increase in the beta-adrenergic inotropic responses
|
vision/eye
• following exposure to 75% oxygen from P7 to P12, extraretinal neovascularization upon return to room air is significantly decreased compared to similarly treated wild-type mice
|
• decrease capillary loss following exposure to 75% oxygen from P7 to P9 compared to similarly treated wild-type mice
• levels of nitrotyrosine in mutants exposed to hyperoxic conditions are not significantly increased compared to room air controls, unlike in wild-type mice
|
limbs/digits/tail
• bone volume is decreased at 6 and 9 weeks of age
• mean trabecular thickness, osteoid surface, osteoblast surface, mineralizing surface, and eroded surface are reduced at 6 weeks of age
|
short femur
(
J:67336
)
• detected at 6, 9 and 18 weeks of age
|
renal/urinary system
• mild glomerular hypercellularity is seen in about 10% of mice at 9 weeks of age
|
skeleton
• after 5 days in culture the number of osteoblasts is significantly reduced compared to wild-type cells
• in culture osteoblasts have decreased alkaline phosphatase activity and form fewer mineralized nodules compared to wild-type cells
• stimulation with 17-beta-estradiol fails to stimulate osteoblast proliferation in culture
• cytokine (TGFB) stimulated migration is attenuated in culture osteoblasts compared to wild-type cells
|
• bone volume is decreased at 6 and 9 weeks of age
• mean trabecular thickness, osteoid surface, osteoblast surface, mineralizing surface, and eroded surface are reduced at 6 weeks of age
|
short femur
(
J:67336
)
• detected at 6, 9 and 18 weeks of age
|
• in the femur, osteoid surface, mineralizing surface, and osteoblast surface are reduced at 6 weeks of age
|
• at 8 weeks of age, femoral/pelvic, spinal, and whole body total bone mineral density are reduced
• however, at 12 weeks of age no significant difference in bone mineral density is detected
|
• mean trabecular thickness in the femur is reduced at 6 and 18 weeks of age
|
• at 6 weeks of age the mineral apposition rate is modestly decreased in the femur
|
growth/size/body
• age related
|
• at P11 mice raised in 16% oxygen (mild hypoxia) weigh less than similarly raised wild-type controls
|
• at 1 year of age
|
respiratory system
• mice raised in mild hypoxia display a decreased vessel volume density compared to similarly raised wild-type controls
|
• mice raised in mild hypoxia display an increased mean lung intercept indicating an increase in intra-alveolar distance and a decreased radial alveolar count compared to similarly raised wild-type controls
|
behavior/neurological
• less helpless (reduced escape latency, fewer failures, and improved avoidance of the aversive stimulus) in a learned helplessness paradigm
• differences are not the result of differences in pain sensitivity, activity level, or anxiety level
|
nervous system
• significant decrease in progenitor cell proliferation
|
• the granule cell layer is increased in volume
|
• decrease in the percentage of pyknotic cells in the brain; however, the number of degenerating cells (detected by Fluoro-Jade B staining) is increased
|
adipose tissue
• increase in the amount of visceral fat at 1 year of age
|
liver/biliary system
• increased accumulation of glycogen is seen predominantly in zone 1 of the liver
|
• hepatocytes in zone one (closest to the artery) contain fewer mitochondria, while hepatocytes in zone 3 contain more mitochondria compared to wild-type cells from the same zone
|
• massive fat deposition is seen in zone 3 of the liver
|
• the ratio of cytosolic citrate synthase activity to NADH-cytochrome c oxidoreductase (KI+III) activity is elevated in liver homogenates
|
cellular
|
• oocytes with an unusually large first polar body are observed
|
|
• a variety of abnormal characteristics noted including enlarged first polar body, cytoplasmic cleavage, blebbing, premature release of the second polar body and cell division
|
|
• fewer oocytes from mutant females reach metaphase II of meiosis but instead remain in metaphase I or become abnormal with an enlarged first polar body, cytoplasmic cleavage, blebbing, and/or premature release of the second polar body
• many of the arrested and abnormal oocytes are also dying
|
• significant decrease in progenitor cell proliferation
|
• after 5 days in culture the number of osteoblasts is significantly reduced compared to wild-type cells
• in culture osteoblasts have decreased alkaline phosphatase activity and form fewer mineralized nodules compared to wild-type cells
• stimulation with 17-beta-estradiol fails to stimulate osteoblast proliferation in culture
• cytokine (TGFB) stimulated migration is attenuated in culture osteoblasts compared to wild-type cells
|
• 42% of pups born to homozygous females are dead by weaning
|