cellular phenotype

• maternal effect
  • all homozygous pups born from homozygous females die within 12 hours of birth; however, homozygous pups born from heterozygous females are viable and fertile
  (MGI Ref ID J:23082)
  • homozygous pups born from homozygous, but not from heterozygous, females display lung dysplasia
  (MGI Ref ID J:23082)

endocrine/exocrine gland phenotype

• abnormal adrenal gland zona fasciculata morphology
  • the zona fasciculata appears atrophied and this atrophy is more severe in homozygous males than in homozygous females
  (MGI Ref ID J:23082)
  • Normal - however, the zona glomerulosa of the adrenal gland and the entire pituitary gland appear normal
  (MGI Ref ID J:23082)

• abnormal adrenal gland morphology
  (MGI Ref ID J:23082)

homeostasis/metabolism phenotype

• abnormal circulating glucose level
  • homozygotes develop hypoglycemia after 24 hours of fasting unlike wild-type mice
  (MGI Ref ID J:23082)

• abnormal circulating corticosterone level
  • increase in plasma levels of corticosterone in response to restraint-induced stress or fasting is severely reduced or absent; this reduction in response is greater in males than in females
  (MGI Ref ID J:23082)

mammalian phenotype

• nervous system phenotype
  • Normal - morphology of the hypothalamic paraventricular nucleus appears normal
  (MGI Ref ID J:23082)

respiratory system phenotype

• abnormal lung morphology
  • homozygous pups born from homozygous females display lung dysplasia with hypercellularity of the lungs, thickened alveolar septae, and fewer air spaces
  (MGI Ref ID J:23082)
  • lung morphology is normal in homozygous pups born from homozygous females given corticosterone during pregnancy and lactation or from heterozygous females
  (MGI Ref ID J:23082)

• abnormal respiratory system physiology
  • alveolar surface tension is increased in homozygous pups born from homozygous females but not in pups born from homozygous females given corticosterone during pregnancy and lactation or heterozygous females
  (MGI Ref ID J:23082)

• thick pulmonary interalveolar septum
  • homozygous pups born from homozygous females display thickened alveolar septae
  (MGI Ref ID J:23082)

behavior/neurological phenotype

• abnormal food intake
  • following a 36 hour fast homozygotes eat less food than wild-type mice
  (MGI Ref ID J:105629)

cellular phenotype

• decreased T cell proliferation
  • proliferation of CD4+ T cells in response to T cell receptor stimuli is decreased compared to wild-type controls
  (MGI Ref ID J:98419)

• increased mesenchymal cell proliferation involved in lung development
  • at E18.5 cell proliferation of proximal mesenchymal cells is increased
  (MGI Ref ID J:53721)

homeostasis/metabolism phenotype

• abnormal circulating glucose level
  • after 36 hours of fasting plasma glucose levels fall unlike in wild-type mice, while plasma insulin levels decrease in both wild-type and homozygous mice
  (MGI Ref ID J:105629)
  • 40 minutes after insulin injection (15 U/kg), fasted female homozygotes have a significantly greater decrease in plasma glucose levels compared to heterozygous females
  (MGI Ref ID J:102987)
  • however, in the absence of insulin injection glucose levels are not significantly lower in fasted male or female homozygotes than in wild-type mice and injection of fasted male
  (MGI Ref ID J:102987)
  • homozygotes with 1 U/kg insulin did not result in a greater reduction in plasma glucose compared to wild-type males
  (MGI Ref ID J:102987)

• decreased circulating corticosterone level
  • plasma corticosterone levels are decreased compared to wild-type mice and do not show the normal diurnal variation in levels
  (MGI Ref ID J:105629)

• decreased circulating leptin level
  • corticosterone supplementation restores the normal fasting induced decrease in leptin levels
  (MGI Ref ID J:105629)
  • plasma leptin levels are decreased compared to wild-type mice and do not show the normal diurnal variation in levels
  (MGI Ref ID J:105629)

• increased circulating interleukin-6 level
  • after intramuscular injection of 100ul turpentine oil plasma IL-6 levels are elevated in 2- to 3-fold more in homozygous mice compared to wild-type mice; plasma IL-6 levels are similar in wild-type and homozygous mice injected with saline
  (MGI Ref ID J:72196)

• abnormal adrenocorticotropin level
  • the increase in plasma adrenocorticotropin levels normally seen during restraint is markedly decreased in homozygotes; however restraint-induced increases in plasma IL-6 levels are similar to wild-type
  (MGI Ref ID J:102987)
  • 40 minutes after insulin-induced hypoglycemia fasted male and female homozygotes do not display an increase in plasma adrenocorticotropin levels unlike fasted wild-type male or heterozygous female mice
  (MGI Ref ID J:102987)
  • adrenocorticotropin levels are elevated in wild-type but not homozygous mice at 1hour after intramuscular injection of 100ul turpentine oil; however no significant induction is seen in either group at most later times
  (MGI Ref ID J:72196)

• abnormal circulating corticosterone level
  • following 5 hours of restraint or food withdrawal the increase in corticosterone levels is decreased compared to wild-type mice; however, changes in lutenizing hormone levels are similar to wild-type mice
  (MGI Ref ID J:54256)
  • following anesthesia and surgery no increase in corticosterone levels is seen unlike in wild-type mice
  (MGI Ref ID J:90690)
  • 40 minutes after insulin induced hypoglycemia fasted female homozygotes do not display an increase in corticosterone levels above that seen in homozygous females after vehicle injection, unlike heterozygous females
  (MGI Ref ID J:102987)
  • 40 minutes after insulin induced hypoglycemia fasted male homozygotes display a attenuated increase in plasma corticosterone compared to wild-type mice
  (MGI Ref ID J:102987)
  • after 36 hours of fasting plasma corticosterone levels do not increase unlike in wild-type mice
  (MGI Ref ID J:105629)
  • corticosterone levels are elevated in wild-type but not homozygous mice for up to 4 hours after intramuscular injection of 100ul turpentine oil; however by 8 hours after injection corticosterone levels are elevated in both groups
  (MGI Ref ID J:72196)
  • fasted male homozygotes have decreased plasma corticosterone compared to wild-type mice
  (MGI Ref ID J:102987)

• abnormal circulating hormone level
  • plasma levels of corticosteroids are about 6-fold lower in homozygotes compared to wild-type mice
  (MGI Ref ID J:90690)

• abnormal circulating adrenaline level
  • after 36 hours of fasting plasma adrenaline levels do not increase unlike in wild-type mice
  (MGI Ref ID J:105629)

• decreased circulating adrenaline level
  • basal and insulin-stimulated epinephrine levels are decrease in homozygous females compared to heterozygotes; however, no significant difference is seen in epinephrine levels between homozygous and wild-type male mice
  (MGI Ref ID J:102987)

• abnormal circulating noradrenaline level
  • after 36 hours of fasting plasma noradrenaline levels do not increase unlike in wild-type mice
  (MGI Ref ID J:105629)

endocrine/exocrine gland phenotype

• abnormal solitary pulmonary neuroendocrine cell morphology
  • at E18.5 in offspring from homozygous crosses, maturation of pulmonary neuroendocrine cells appears delayed
  (MGI Ref ID J:53721)

immune system phenotype

• decreased susceptibility to experimental autoimmune encephalomyelitis
  • severity of experimental autoimmune encephalomyelitis is reduced in homozygotes (mean maximal score 0.081 +/- 0.9 versus 1.71 +/- 0.8 in wild-type mice); this includes reduced infiltration of CD4+ cells and marcophages in to the central nervous system
  (MGI Ref ID J:98419)
  • incidence of experimental autoimmune encephalomyelitis is reduced in homozygotes but the time of onset is similar to wild-type
  (MGI Ref ID J:98419)

• abnormal cell-mediated immunity
  (MGI Ref ID J:98419)

• decreased inflammatory response
  • leukocyte infiltration after intramuscular injection of 100ul turpentine oil is significantly less in homozygotes compared to wild-type mice
  (MGI Ref ID J:72196)
  • injection of ileal loops with purified toxin A results in a significantly smaller increase in fluid secretion, reduced epithelial damage, congestion and edema, decreased neutrophil infiltration, and no increase in TAC1 levels or immunostaining in homozygotes
  (MGI Ref ID J:90690)
  • tes
  (MGI Ref ID J:90690)

• decreased T cell proliferation
  • proliferation of CD4+ T cells in response to T cell receptor stimuli is decreased compared to wild-type controls
  (MGI Ref ID J:98419)

• increased circulating interleukin-6 level
  • after intramuscular injection of 100ul turpentine oil plasma IL-6 levels are elevated in 2- to 3-fold more in homozygous mice compared to wild-type mice; plasma IL-6 levels are similar in wild-type and homozygous mice injected with saline
  (MGI Ref ID J:72196)

• abnormal cytokine secretion
  • purified CD4+ T cells stimulated with antigen presenting cells produce less IL2 and IFNG suggesting a defect in T cell receptor stimulated activation
  (MGI Ref ID J:98419)
  • purified CD4+ T cells stimulated with low concentrations of anti-CD3/anti-CD28 antibodies (strong stimulus) or any concentration of myelin oligodendrocyte glycoprotein peptide (weak stimulus) produce more IL5
  (MGI Ref ID J:98419)

• increased splenocyte number
  • naive homozygotes have in increased number of splenocytes however no difference is seen between homozygotes and wild-type mice after immunization
  (MGI Ref ID J:98419)

• abnormal professional antigen presenting cell physiology
  • homozygous antigen presenting cells incubated with a myelin oligodendrocyte glycoprotein peptide induce less proliferation of wild-type CD4+ T cells compared to wild-type antigen presenting cells
  (MGI Ref ID J:98419)

• abnormal inflammatory response
  (MGI Ref ID J:98419)

integument phenotype

• abnormal epidermis stratum corneum morphology
  • supplementation of homozygous females with corticosterone during pregnancy rescues the delay in stratum corneum development in homozygous pups
  (MGI Ref ID J:49863)
  • at E17.5 in offspring from homozygous crosses, the stratum corneum is absent or if present is only 1 cell layer thick and lacks the normal membrane localization of polar lipids and organization of lamellar body-derived material into lamellar structures
  (MGI Ref ID J:49863)
  • however, at birth a normal multilayered stratum corneum is present
  (MGI Ref ID J:49863)

• abnormal epidermis stratum granulosum morphology
  • supplementation of homozygous females with corticosterone during pregnancy rescues the delay in granular layer development in homozygous pups
  (MGI Ref ID J:49863)
  • at E17.5 in offspring from homozygous crosses, the granular is absent; however, a normal granular layer is present at birth
  (MGI Ref ID J:49863)

growth/size/body region phenotype

• abnormal body weight
  • during a 36 hour fast homozygotes lose less weight and after fasting gain the weight back more slowly compared to wild-type mice
  (MGI Ref ID J:105629)

nervous system phenotype

• abnormal circulating adrenaline level
  • after 36 hours of fasting plasma adrenaline levels do not increase unlike in wild-type mice
  (MGI Ref ID J:105629)

• abnormal circulating noradrenaline level
  • after 36 hours of fasting plasma noradrenaline levels do not increase unlike in wild-type mice
  (MGI Ref ID J:105629)

• abnormal solitary pulmonary neuroendocrine cell morphology
  • at E18.5 in offspring from homozygous crosses, maturation of pulmonary neuroendocrine cells appears delayed
  (MGI Ref ID J:53721)

• decreased circulating adrenaline level
  • basal and insulin-stimulated epinephrine levels are decrease in homozygous females compared to heterozygotes; however, no significant difference is seen in epinephrine levels between homozygous and wild-type male mice
  (MGI Ref ID J:102987)

respiratory system phenotype

• abnormal surfactant composition
  • at E17.5 in offspring from homozygous crosses, expression of some surfactant proteins is reduced and the concentration of dipalmitoyl phosphatidylcholine (DPPC, a surfact lipid commonly used to indicate lung maturity) in amniotic fluid is decreased; however, by E18.5 amniotic levels of DPPC are similar to wild-type
  (MGI Ref ID J:53721)
  • er, by E18.5 amniotic levels of DPPC are similar to wild-type
  (MGI Ref ID J:53721)

• abnormal club cell morphology
  • at E18.5 in offspring from homozygous crosses, maturation of Clara cells appears delayed
  (MGI Ref ID J:53721)

• abnormal lung development
  • at E17.5 and E18.5 in offspring from homozygous crosses, lung retain an immature dense pseudoglandular appearance with little or no formation of airspaces unlike wild-type mice
  (MGI Ref ID J:53721)
  • at E17.5 and E18.5 in offspring from homozygous crosses, lung wet and dry weight and total DNA content are increased and at E18.5 cell proliferation of proximal and distal epithelial cells and proximal mesenchymal cells is increased
  (MGI Ref ID J:53721)
  • at E18.5 in offspring from homozygous crosses, maturation of Clara and pulmonary neuroendocrine cells appears delayed
  (MGI Ref ID J:53721)

• increased mesenchymal cell proliferation involved in lung development
  • at E18.5 cell proliferation of proximal mesenchymal cells is increased
  (MGI Ref ID J:53721)

hematopoietic system phenotype

• increased splenocyte number
  • naive homozygotes have in increased number of splenocytes however no difference is seen between homozygotes and wild-type mice after immunization
  (MGI Ref ID J:98419)

• decreased T cell proliferation
  • proliferation of CD4+ T cells in response to T cell receptor stimuli is decreased compared to wild-type controls
  (MGI Ref ID J:98419)