Phenotypes associated with this allele

• Allele Symbol: Adam17^tm1Imx
• Allele Name: targeted mutation 1, Immunex
• Allele ID: MGI:1857753
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Adam17^tm1Imx/Adam17^tm1Imx	B6.129-Adam17^tm1Imx	MGI:5284894
hm2	Adam17^tm1Imx/Adam17^tm1Imx	involves: 129 * C57BL/6	MGI:2174923
hm3	Adam17^tm1Imx/Adam17^tm1Imx	involves: 129 * C57BL/6J	MGI:3622269
hm4	Adam17^tm1Imx/Adam17^tm1Imx	involves: 129 * DBA/1J	MGI:4947980
ht5	Adam17^tm1Imx/Adam17^woe	involves: 129 * C57BL/6	MGI:4457888
cx6	Adam17^tm1Imx/Adam17^tm1Imx Adam19^Gt(Betageo)1Bbl/Adam19^Gt(Betageo)1Bbl	involves: 129/Sv * 129P2/OlaHsd * C57BL/6	MGI:3654837
cx7	Adam12^tm1Asf/Adam12^tm1Asf Adam15^tm1Bbl/Adam15^tm1Bbl Adam17^tm1Imx/Adam17^tm1Imx Adam9^tm1Bbl/Adam9^tm1Bbl	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3056935

Genotype
MGI:5284894

hm1

• Allelic Composition: Adam17^tm1Imx/Adam17^tm1Imx
• Genetic Background: B6.129-Adam17^tm1Imx

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

immune system

enhanced leukocyte tethering or rolling ( J:174865 )

• in a model of sterile peritonitis irradiated, wild-type mice reconstituted with fetal liver cells exhibit accelerated neutrophil recruitment compared to in wild-type mice reconstituted with wild-type cells

• in vivo, irradiated wild-type mice reconstituted with fetal liver cells exhibit decreased leukocyte rolling velocity and increased adhesion compared to in wild-type mice reconstituted with wild-type cells

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:174865 )

• irradiated wild-type mice reconstituted with fetal liver cells fail to exhibit an increase in peritoneal neutrophils in response to treatment with hydroxamate inhibitor unlike similarly treated wild-type mice reconstituted with wild-type cells

cellular

enhanced leukocyte tethering or rolling ( J:174865 )

• in a model of sterile peritonitis irradiated, wild-type mice reconstituted with fetal liver cells exhibit accelerated neutrophil recruitment compared to in wild-type mice reconstituted with wild-type cells

• in vivo, irradiated wild-type mice reconstituted with fetal liver cells exhibit decreased leukocyte rolling velocity and increased adhesion compared to in wild-type mice reconstituted with wild-type cells

hematopoietic system

enhanced leukocyte tethering or rolling ( J:174865 )

• in a model of sterile peritonitis irradiated, wild-type mice reconstituted with fetal liver cells exhibit accelerated neutrophil recruitment compared to in wild-type mice reconstituted with wild-type cells

• in vivo, irradiated wild-type mice reconstituted with fetal liver cells exhibit decreased leukocyte rolling velocity and increased adhesion compared to in wild-type mice reconstituted with wild-type cells

Genotype
MGI:2174923

hm2

• Allelic Composition: Adam17^tm1Imx/Adam17^tm1Imx
• Genetic Background: involves: 129 * C57BL/6

mortality/aging

premature death ( J:51053 )

• a few animals survived for 3 weeks after birth

perinatal lethality, incomplete penetrance ( J:51053 )

• most animals died between E17.5 and P1

• most animals found alive at birth died within several hours

pigmentation

abnormal coat/hair pigmentation ( J:51053 )

• irregular and dense pigmentation patterns within pelage hairs

embryo

abnormal embryonic tissue morphology ( J:51053 )

• delayed epithelial maturation of the intestine, lung, nonglandular stomach, thyroid, parathyroid, and salivary gland

abnormal trophoblast layer morphology ( J:51053 )

• mild attenuation of the spongiotrophoblast layer associated with a disorganized and discontinuous plate of giant trophoblast cells

decreased spongiotrophoblast size ( J:51053 )

• attenuation of the spongiotrophoblast layer

growth/size/body

enlarged heart ( J:85547 )

• a >2-fold increase in fetal heart size, including both atria and ventricles, was observed after E18.5

• cardiac enlargement reached a maximum on P1, when most mutant mice died

increased heart weight ( J:85547 )

• at E18.5, homozygotes showed a 20%-30% increase in heart weight-to-body weight ratio relative to wild-type or heterozygous mutant mice

decreased body size ( J:51053 )

• the few animals that survived weighed 20%-40% less than wild-type

immune system

increased incidence of corneal inflammation ( J:51053 )

• surviving animals had corneal inflammation

vision/eye

increased incidence of corneal inflammation ( J:51053 )

• surviving animals had corneal inflammation

abnormal eye morphology ( J:51053 )

• surviving animals show eye degeneration

abnormal conjunctival sac morphology ( J:51053 )

• lacked a conjunctival sac

abnormal cornea morphology ( J:51053 )

• attenuated corneas

failure of eyelid fusion ( J:51053 )

• at E17.5, all fetuses had open eyelids due to failure of eyelid fusion

eyelids open at birth ( J:51053 )

• all newborns were readily identified by their open eyelids

cardiovascular system

increased myocardial fiber size ( J:85547 )

• at P1, mutant cardiomyocytes were enlarged and were more loosely packed, with larger extracellular spaces

• however, no excessive collagen deposits or chamber septation abnormalities were observed

abnormal trabecula carnea morphology ( J:85547 )

• at E18.5, the enlarged ventricles and thickened myocardium displayed deep trabecular recesses

• enlarged fetal hearts with increased myocardial trabeculation and reduced cell compaction resemble pathological changes of noncompaction of ventricular myocardium

ventricular septal defect ( J:99649 )

• exhibit a ventricular septal defect

enlarged heart ( J:85547 )

• a >2-fold increase in fetal heart size, including both atria and ventricles, was observed after E18.5

• cardiac enlargement reached a maximum on P1, when most mutant mice died

increased heart weight ( J:85547 )

• at E18.5, homozygotes showed a 20%-30% increase in heart weight-to-body weight ratio relative to wild-type or heterozygous mutant mice

thick aortic valve ( J:99649 )

• thicker aortic valve

thick ventricular wall ( J:85547 )

• at E18.5, the ventricular wall, esp. the trabecular layer, was thicker than wild-type

abnormal fetal cardiomyocyte proliferation ( J:85547 )

• at P1, the cell proliferation index in mutant hearts was 14 3% versus 8 1% in wild-type hearts; no differences were observed at E16.5

• no significant differences in cell apoptosis were noted in mutant hearts at P1

muscle

increased myocardial fiber size ( J:85547 )

• at P1, mutant cardiomyocytes were enlarged and were more loosely packed, with larger extracellular spaces

• however, no excessive collagen deposits or chamber septation abnormalities were observed

abnormal trabecula carnea morphology ( J:85547 )

• at E18.5, the enlarged ventricles and thickened myocardium displayed deep trabecular recesses

• enlarged fetal hearts with increased myocardial trabeculation and reduced cell compaction resemble pathological changes of noncompaction of ventricular myocardium

abnormal fetal cardiomyocyte proliferation ( J:85547 )

• at P1, the cell proliferation index in mutant hearts was 14 3% versus 8 1% in wild-type hearts; no differences were observed at E16.5

• no significant differences in cell apoptosis were noted in mutant hearts at P1

digestive/alimentary system

abnormal small intestine morphology ( J:51053 )

• proximal small intestine shows variably blunted villi and a hypercellular, pseudostratified mucosal epithelium displaying less cell polarity, at E17.5

respiratory system

abnormal bronchiole epithelium morphology ( J:51053 )

• E17.5 embroys show impaired differentiation of the bronchiolar epithelium

• bronchioles are lined by epithelium that appears disorganized with variable hypercellularity, segmental stratification, and increased nuclear to cytoplasmic ratio

integument

abnormal coat/hair pigmentation ( J:51053 )

• irregular and dense pigmentation patterns within pelage hairs

abnormal hair follicle morphology ( J:51053 )

• surviving animals had irregular hair follicle structure and distribution, hair follicles extended into adipose layer

abnormal hair follicle orientation ( J:51053 )

• surviving animals had irrigular hair follicle orientation

curly vibrissae ( J:51053 )

• surviving animals had curly vibrissae

short vibrissae ( J:51053 )

cellular

abnormal fetal cardiomyocyte proliferation ( J:85547 )

• at P1, the cell proliferation index in mutant hearts was 14 3% versus 8 1% in wild-type hearts; no differences were observed at E16.5

• no significant differences in cell apoptosis were noted in mutant hearts at P1

Genotype
MGI:3622269

hm3

• Allelic Composition: Adam17^tm1Imx/Adam17^tm1Imx
• Genetic Background: involves: 129 * C57BL/6J

Adam17^tm1Imx/Adam17^tm1Imx embryos develop internal hemorrhage

cardiovascular system

abnormal blood vessel morphology ( J:166217 )

• at E17.5, hemorrhaging is accompanied by a loss of the vascular organization

abnormal brain vasculature morphology ( J:166217 )

• at E14.5, the large cranial vessels projecting posteriorly over the midbrain region show disruption of the elaborate branching pattern observed in controls, with shorter and less elaborate branching and abnormal fusion of vessels at various branch points not observed in controls

enlarged atrioventricular valve ( J:83820 )

• newborn homozygotes displayed enlarged atrioventricular valves

enlarged semilunar valve ( J:83820 )

• newborn homozygotes displayed enlarged semilunar valves

enlarged aortic valve ( J:83820 )

• at P1, the mean area of mutant aortic valves was 57.5 +/- 29.4 mm² relative to 20.0 +/- 7.4 mm² observed in wild-type aortic valves

enlarged pulmonary valve ( J:83820 )

internal hemorrhage ( J:166217 )

• 50% and 67% of E14.5 and E17.5 embryos, respectively, exhibit internal hemorrhaging, however no hemorrhagic lesions on the yolk sack vasculature are seen

• hemorrhaging between E11.5 and E14.5 localizes primarily on the side of the head and extent and localization of bleeding progresses with age

integument

nuchal edema ( J:166217 )

• at E17.5, mutants show signs of edema on the neck and the upper back area

growth/size/body

nuchal edema ( J:166217 )

• at E17.5, mutants show signs of edema on the neck and the upper back area

decreased body length ( J:166217 )

• fetuses at E14.5 and E17.5 tend to be shorter in length compared to controls, however the differences are not significant

decreased fetal weight ( J:166217 )

• fetuses at E14.5 and E17.5 tend to be underweight compared to controls, however the differences are not significant

homeostasis/metabolism

nuchal edema ( J:166217 )

• at E17.5, mutants show signs of edema on the neck and the upper back area

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:166217 )

• 50% die at E17.5, however no mortality is seen at E11.5 or E14.5

nervous system

abnormal brain vasculature morphology ( J:166217 )

• at E14.5, the large cranial vessels projecting posteriorly over the midbrain region show disruption of the elaborate branching pattern observed in controls, with shorter and less elaborate branching and abnormal fusion of vessels at various branch points not observed in controls

Genotype
MGI:4947980

hm4

• Allelic Composition: Adam17^tm1Imx/Adam17^tm1Imx
• Genetic Background: involves: 129 * DBA/1J

mortality/aging

neonatal lethality, complete penetrance ( J:68672 )

• mice die shortly after birth due to respiratory failure

vision/eye

failure of eyelid fusion ( J:68672 )

• fetuses (E16.5 or older) display open eyelids

eyelids open at birth ( J:68672 )

• at P0, newborn mice are reliably identified by an open eyelid phenotype

homeostasis/metabolism

cyanosis ( J:68672 )

• newborn (P0) mice are cyanotic in skin color

respiratory system

abnormal lung morphology ( J:68672 )

• neonatal lungs have a semitranslucent gross appearance

abnormal lung vasculature morphology ( J:68672 )

• the peripheral lung vascular network is underdeveloped, as determined by reduced PECAM-1 staining

• only sporadic PECAM-1-positive endothelial cells are found in thickened lung mesenchyme

• at E16.5, mutant lungs have ~60% fewer capillary branch points than control lungs

abnormal lung development ( J:68672 )

• at P0, large and dilated airways are observed in the lung periphery, with fewer septations and thickened interstitial tissue, indicating delayed lung development

• PCNA proliferative indices are reduced by 64% and 40% at E16.5 and E18, respectively, in the bronchial epithelium

abnormal branching involved in lung morphogenesis ( J:68672 )

• at E16.5, sparse air spaces with abundant mesenchyme reminiscent of the early pseudoglandular stage are seen, unlike in wild-type lungs where a normal branching pattern with regularly shaped terminal tubules is observed

• when placed in serum-free organ culture, E12 lung primordia from mutant mice branch poorly with only 51.5% the number of peripheral terminal buds seen in wild-type controls

abnormal lung saccule morphology ( J:68672 )

• at E18, fewer saccular structures, thickened interstitial mesenchyme and no septal formation are observed, instead of the characteristic thin-walled terminal buds with extending septa seen in wild-type lungs

• at E16.5 and E18, mutant lungs display 56% and 38% less distal airway spaces relative to wild-type lungs

thick lung-associated mesenchyme ( J:68672 )

• a thickened lung mesenchymal tissue is observed at E18 and P0

abnormal lung epithelium morphology ( J:68672 )

• fewer PCNA staining-positive epithelial cells are detected at E16.5 and E18

• PCNA proliferative indices are reduced by 64% and 40% at E16.5 and E18, respectively

• at E16.5, a reduced SP-C immunostaining intensity is detected in the fewer distal epithelial branches indicating a delay in (prealveolar type II) epithelial cell differentiation

• only weak SP-C staining is seen in some peripheral epithelial cells of dilated airways in cultured E12 mutant lungs

• both lung hypoplasia and delayed epithelial cell differentiation can be rescued by exogenous addition of soluble stimulatory factors including TNF or EGF in embryonic lung culture

pulmonary hypoplasia ( J:68672 )

• neonatal lungs are hypoplastic

abnormal respiratory conducting tube morphology ( J:68672 )

• at P0, fewer, but dilated, terminal airways are observed in the lung periphery

• fewer airways of irregular shape are also seen in the proximal area with apparently thickened mesenchymal tissue

dilated respiratory conducting tube ( J:68672 )

• at P0, large terminal airways are dilated

pale lung ( J:68672 )

• neonatal lungs are pale in color

respiratory distress ( J:68672 )

• newborn (P0) mice show obvious breathing difficulties

respiratory failure ( J:68672 )

• at P0

cardiovascular system

abnormal lung vasculature morphology ( J:68672 )

• the peripheral lung vascular network is underdeveloped, as determined by reduced PECAM-1 staining

• only sporadic PECAM-1-positive endothelial cells are found in thickened lung mesenchyme

• at E16.5, mutant lungs have ~60% fewer capillary branch points than control lungs

Genotype
MGI:4457888

ht5

• Allelic Composition: Adam17^tm1Imx/Adam17^woe
• Genetic Background: involves: 129 * C57BL/6

vision/eye

abnormal eye morphology ( J:160781 )

• authors state that mice exhibit similar phenotypes as observed in Adam17^woe homozygotes

eyelids open at birth ( J:160781 )

integument

abnormal coat/ hair morphology ( J:160781 )

• authors state that mice exhibit similar phenotypes as observed in Adam17^woe homozygotes

Genotype
MGI:3654837

cx6

• Allelic Composition: Adam17^tm1Imx/Adam17^tm1Imx; Adam19^{Gt(Betageo)1Bbl}/Adam19^{Gt(Betageo)1Bbl}
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * C57BL/6

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:99649 )

• die around E13.5 to E14.5

cardiovascular system

abnormal myocardium layer morphology ( J:99649 )

• 6 of 7 embryos at E13.5-14.5 show an underdeveloped myocardial wall, especially of the left ventricle

absent myocardial trabeculae ( J:99649 )

• 6 of 7 embryos at E13.5-14.5 show severe lack of trabeculation

thin ventricular wall ( J:99649 )

muscle

abnormal myocardium layer morphology ( J:99649 )

• 6 of 7 embryos at E13.5-14.5 show an underdeveloped myocardial wall, especially of the left ventricle

absent myocardial trabeculae ( J:99649 )

• 6 of 7 embryos at E13.5-14.5 show severe lack of trabeculation

Genotype
MGI:3056935

cx7

• Allelic Composition: Adam12^tm1Asf/Adam12^tm1Asf; Adam15^tm1Bbl/Adam15^tm1Bbl; Adam17^tm1Imx/Adam17^tm1Imx; Adam9^tm1Bbl/Adam9^tm1Bbl
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

neonatal lethality ( J:88801 )

cardiovascular system

abnormal mitral valve morphology ( J:88801 )

• thickened and misshapen valves

thick mitral valve ( J:88801 )

abnormal tricuspid valve morphology ( J:88801 )

• thickened and misshapen valves

thick tricuspid valve ( J:88801 )

abnormal aortic valve morphology ( J:88801 )

• thickened and misshapen valves

thick aortic valve ( J:88801 )

abnormal pulmonary valve morphology ( J:88801 )

• thickened and misshapen valves

thick pulmonary valve ( J:88801 )

vision/eye

eyelids open at birth ( J:88801 )