Phenotypes associated with this allele

• Allele Symbol: Crh^tm1Maj
• Allele Name: targeted mutation 1, Joseph Majzoub
• Allele ID: MGI:1857392
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Crh^tm1Maj/Crh^tm1Maj	involves: 129S2/SvPas * C57BL/6	MGI:3622559
hm2	Crh^tm1Maj/Crh^tm1Maj	involves: 129S2/SvPas * C57BL/6J	MGI:3622558
cx3	Crh^tm1Maj/Crh^+ Tg(MECP2)1Hzo/0	involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:5314414

Genotype
MGI:3622559

hm1

• Allelic Composition: Crh^tm1Maj/Crh^tm1Maj
• Genetic Background: involves: 129S2/SvPas * C57BL/6

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

respiratory system

abnormal lung development ( J:53721 )

• 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

• 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

• at E18.5 in offspring from homozygous crosses, maturation of Clara and pulmonary neuroendocrine cells appears delayed

increased mesenchymal cell proliferation involved in lung development ( J:53721 )

• at E18.5 cell proliferation of proximal mesenchymal cells is increased

abnormal club cell morphology ( J:53721 )

• at E18.5 in offspring from homozygous crosses, maturation of Clara cells appears delayed

abnormal surfactant composition ( J:53721 )

• 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

homeostasis/metabolism

abnormal circulating glucose level ( J:102987 , 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 (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 (J:102987)

• homozygotes with 1 U/kg insulin did not result in a greater reduction in plasma glucose compared to wild-type males (J:102987)

• 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 (J:105629)

abnormal circulating hormone level ( J:90690 )

• plasma levels of corticosteroids are about 6-fold lower in homozygotes compared to wild-type mice

abnormal circulating adrenaline level ( J:105629 )

• after 36 hours of fasting plasma adrenaline levels do not increase unlike in wild-type mice

decreased circulating adrenaline level ( J:102987 )

• 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

abnormal circulating corticosterone level ( J:54256 , J:72196 , J:90690 , J:102987 , J:105629 )

• 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 (J:54256)

• 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 (J:72196)

• following anesthesia and surgery no increase in corticosterone levels is seen unlike in wild-type mice (J:90690)

• fasted male homozygotes have decreased plasma corticosterone compared to wild-type mice (J:102987)

• 40 minutes after insulin induced hypoglycemia fasted male homozygotes display a attenuated increase in plasma corticosterone compared to wild-type mice (J:102987)

• 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 (J:102987)

• after 36 hours of fasting plasma corticosterone levels do not increase unlike in wild-type mice (J:105629)

decreased circulating corticosterone level ( J:105629 )

• plasma corticosterone levels are decreased compared to wild-type mice and do not show the normal diurnal variation in levels

decreased circulating leptin level ( J:105629 )

• plasma leptin levels are decreased compared to wild-type mice and do not show the normal diurnal variation in levels

• corticosterone supplementation restores the normal fasting induced decrease in leptin levels

abnormal circulating noradrenaline level ( J:105629 )

• after 36 hours of fasting plasma noradrenaline levels do not increase unlike in wild-type mice

increased circulating interleukin-6 level ( J:72196 )

• 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

abnormal adrenocorticotropin level ( J:72196 , 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 (J:72196)

• 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 (J:102987)

• 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 (J:102987)

immune system

increased splenocyte number ( J:98419 )

• naive homozygotes have in increased number of splenocytes however no difference is seen between homozygotes and wild-type mice after immunization

increased circulating interleukin-6 level ( J:72196 )

• 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

abnormal cell-mediated immunity ( J:98419 )

decreased T cell proliferation ( J:98419 )

• proliferation of CD4+ T cells in response to T cell receptor stimuli is decreased compared to wild-type controls

abnormal professional antigen presenting cell physiology ( J:98419 )

• 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

abnormal cytokine secretion ( J:98419 )

• purified CD4+ T cells stimulated with antigen presenting cells produce less IL2 and IFNG suggesting a defect in T cell receptor stimulated activation

• 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

decreased susceptibility to experimental autoimmune encephalomyelitis ( J:98419 )

• 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

• incidence of experimental autoimmune encephalomyelitis is reduced in homozygotes but the time of onset is similar to wild-type

abnormal inflammatory response ( J:98419 )

decreased inflammatory response ( J:72196 , J:90690 )

• leukocyte infiltration after intramuscular injection of 100ul turpentine oil is significantly less in homozygotes compared to wild-type mice (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 (J:90690)

growth/size/body

abnormal body weight ( J:105629 )

• during a 36 hour fast homozygotes lose less weight and after fasting gain the weight back more slowly compared to wild-type mice

behavior/neurological

abnormal food intake ( J:105629 )

• following a 36 hour fast homozygotes eat less food than wild-type mice

hematopoietic system

decreased T cell proliferation ( J:98419 )

• proliferation of CD4+ T cells in response to T cell receptor stimuli is decreased compared to wild-type controls

increased splenocyte number ( J:98419 )

• naive homozygotes have in increased number of splenocytes however no difference is seen between homozygotes and wild-type mice after immunization

integument

abnormal epidermis stratum corneum morphology ( 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

• however, at birth a normal multilayered stratum corneum is present

• supplementation of homozygous females with corticosterone during pregnancy rescues the delay in stratum corneum development in homozygous pups

abnormal epidermis stratum granulosum morphology ( J:49863 )

• at E17.5 in offspring from homozygous crosses, the granular is absent; however, a normal granular layer is present at birth

• supplementation of homozygous females with corticosterone during pregnancy rescues the delay in granular layer development in homozygous pups

endocrine/exocrine glands

abnormal solitary pulmonary neuroendocrine cell morphology ( J:53721 )

• at E18.5 in offspring from homozygous crosses, maturation of pulmonary neuroendocrine cells appears delayed

nervous system

abnormal solitary pulmonary neuroendocrine cell morphology ( J:53721 )

• at E18.5 in offspring from homozygous crosses, maturation of pulmonary neuroendocrine cells appears delayed

cellular

decreased T cell proliferation ( J:98419 )

• proliferation of CD4+ T cells in response to T cell receptor stimuli is decreased compared to wild-type controls

increased mesenchymal cell proliferation involved in lung development ( J:53721 )

• at E18.5 cell proliferation of proximal mesenchymal cells is increased

Genotype
MGI:3622558

hm2

• Allelic Composition: Crh^tm1Maj/Crh^tm1Maj
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

cellular

maternal effect ( J:23082 )

• all homozygous pups born from homozygous females die within 12 hours of birth; however, homozygous pups born from heterozygous females are viable and fertile

• homozygous pups born from homozygous, but not from heterozygous, females display lung dysplasia

respiratory system

abnormal lung morphology ( J:23082 )

• homozygous pups born from homozygous females display lung dysplasia with hypercellularity of the lungs, thickened alveolar septae, and fewer air spaces

• lung morphology is normal in homozygous pups born from homozygous females given corticosterone during pregnancy and lactation or from heterozygous females

thick pulmonary interalveolar septum ( J:23082 )

• homozygous pups born from homozygous females display thickened alveolar septae

abnormal respiratory system physiology ( J:23082 )

• 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

homeostasis/metabolism

abnormal circulating glucose level ( J:23082 )

• homozygotes develop hypoglycemia after 24 hours of fasting unlike wild-type mice

abnormal circulating corticosterone level ( J:23082 )

• 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

endocrine/exocrine glands

abnormal adrenal gland morphology ( J:23082 )

decreased adrenal gland zona fasciculata size ( J:23082 )

• the zona fasciculata appears atrophied and this atrophy is more severe in homozygous males than in homozygous females

• however, the zona glomerulosa of the adrenal gland and the entire pituitary gland appear normal

nervous system

nervous system phenotype ( J:23082 )

N • morphology of the hypothalamic paraventricular nucleus appears normal

Genotype
MGI:5314414

cx3

• Allelic Composition: Crh^tm1Maj/Crh⁺; Tg(MECP2)1Hzo/0
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6 * FVB/N

behavior/neurological

abnormal anxiety-related response ( J:181213 )

• anxiety-like behavior is reduced compared to single Tg(MECP2)1Hzo hemizygous mice, with double mutants being less anxious in the elevated plus maze and the light/dark box

homeostasis/metabolism

abnormal corticosterone level ( J:181213 )

• mutants exhibit a decrease in stress-induced serum corticosterone levels from that seen in single Tg(MECP2)1Hzo hemizygous mice