Phenotypes associated with this allele

• Allele Symbol: Igf1^tm1Arge
• Allele Name: targeted mutation 1, Argiris Efstratiadis
• Allele ID: MGI:1926485
• Summary: 17 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Igf1^tm1Arge/Igf1^tm1Arge	either: 129S/SvEv-Igf1^tm1Arge or (involves: 129S/SvEv * C57BL/6J) or (involves: 129S/SvEv * MF1)	MGI:2175078
hm2	Igf1^tm1Arge/Igf1^tm1Arge	involves: 129S/SvEv	MGI:4834805
hm3	Igf1^tm1Arge/Igf1^tm1Arge	involves: 129S/SvEv * DBA * MF1	MGI:4456248
hm4	Igf1^tm1Arge/Igf1^tm1Arge	involves: 129S/SvEv * MF1	MGI:3688508
ht5	Igf1^tm1Arge/Igf1^+	involves: 129S/SvEv * MF1	MGI:3696122
cx6	Igf1^tm1Arge/Igf1^tm1Arge Igf1r^tm1Arge/Igf1r^tm1Arge	either: (involves: 129S/SvEv) or (involves: 129S/SvEv * C57BL/6J) or (involves: 129S/SvEv * MF1)	MGI:3629674
cx7	Igf1^tm1Arge/Igf1^tm1Arge Igf2^tm1Rob/Igf2^+	either: (involves: 129S/SvEv) or (involves: 129S/SvEv * C57BL/6J) or (involves: 129S/SvEv * MF1)	MGI:3629689
cx8	Igf1^tm1Arge/Igf1^+ Lif^tm1Stw/Lif^tm1Stw	involves: 129S/SvEv * 129S1/Sv	MGI:4834804
cx9	Igf1^tm1Arge/Igf1^tm1Arge Lif^tm1Stw/Lif^tm1Stw	involves: 129S/SvEv * 129S1/Sv	MGI:4834806
cx10	Igf1^tm1Arge/Igf1^+ Lif^tm1Stw/Lif^tm1Stw	involves: 129S/SvEv * 129S1/Sv * BALB/c * C57BL/6J * MF1	MGI:4834783
cx11	Igf1^tm1Arge/Igf1^tm1Arge Lif^tm1Stw/Lif^+	involves: 129S/SvEv * 129S1/Sv * BALB/c * C57BL/6J * MF1	MGI:4834785
cx12	Igf1^tm1Arge/Igf1^tm1Arge Lif^tm1Stw/Lif^tm1Stw	involves: 129S/SvEv * 129S1/Sv * BALB/c * C57BL/6J * MF1	MGI:4834786
cx13	Gpc3^tm1Arge/Gpc3^tm1Arge Igf1^tm1Arge/Igf1^tm1Arge	involves: 129S/SvEv * 129S1/Sv * C57BL/6J * DBA * MF1	MGI:3629898
cx14	Gpc3^tm1Arge/Y Igf1^tm1Arge/Igf1^tm1Arge	involves: 129S/SvEv * 129S1/Sv * C57BL/6J * DBA * MF1	MGI:3629900
cx15	Igf1^tm1Arge/Igf1^+ Lif^tm1Stw/Lif^tm1Stw	involves: 129S/SvEv * 129S1/Sv * C57BL/6 * MF1	MGI:4834891
cx16	Igf1^tm1Arge/Igf1^+ Lif^tm1Stw/Lif^+	involves: 129S/SvEv * 129S1/Sv * C57BL/6 * MF1	MGI:4834892
cx17	Ghr^tm1Arge/Ghr^tm1Arge Igf1^tm1Arge/Igf1^tm1Arge	involves: 129S/SvEv * C57BL/6J * DBA * MF1	MGI:4456249

Genotype
MGI:2175078

hm1

• Allelic Composition: Igf1^tm1Arge/Igf1^tm1Arge
• Genetic Background: either: 129S/SvEv-Igf1^tm1Arge or (involves: 129S/SvEv * C57BL/6J) or (involves: 129S/SvEv * MF1)

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

mortality/aging

neonatal lethality, complete penetrance ( J:15108 )

• Background Sensitivity: moderate to severe, strain dependent: 10% of129S6/SvEvTac congenic homozygous animals and 16% of (129S6/SvEvTac x C57BL/6J)F2 homozygous animals survive to adulthood while 68% of (129S6/SvEvTac x MF1) homozygous animals survive to adulthood

• death usually occurs between 15 min and 6 hours after birth

growth/size/body

decreased body size ( J:15108 )

• about 25% of recovered neonates exhibit a birthweight approximately 60% of normal

postnatal growth retardation ( J:15108 )

skeleton

delayed bone ossification ( J:15108 )

• ossification is only slightly delayed and does not differ from that of Igf2^tm1Rob mutants

Genotype
MGI:4834805

hm2

• Allelic Composition: Igf1^tm1Arge/Igf1^tm1Arge
• Genetic Background: involves: 129S/SvEv

nervous system

decreased motor neuron number ( J:103711 )

• at E18.5, mice exhibit reduced motor neurons in the brainstem nuclei (trigeminal and facial nuclei ) compared with wild-type mice

Genotype
MGI:4456248

hm3

• Allelic Composition: Igf1^tm1Arge/Igf1^tm1Arge
• Genetic Background: involves: 129S/SvEv * DBA * MF1

growth/size/body

proportional dwarf ( J:66913 )

postnatal growth retardation ( J:66913 )

• weight at birth and P10 is normal, however after 2 weeks post birth, mice are growth retarded

homeostasis/metabolism

increased circulating growth hormone level ( J:66913 )

skeleton

abnormal long bone epiphyseal plate proliferative zone ( J:66913 )

• proliferative zone of chondrocytes is shorter at p22 and p30

• chondrocyte proliferation in the proliferative zone is 63% of wild-type

abnormal long bone hypertrophic chondrocyte zone ( J:66913 )

• reduction in the rate of production and maturation of hypertrophic zone chondrocytes

decreased width of hypertrophic chondrocyte zone ( J:66913 )

• hypertrophic zones of chondrocytes are shorter at p22 and p30

abnormal trabecular bone morphology ( J:66913 )

• reduction in the height of the primary spongiosa

abnormal chondrocyte morphology ( J:66913 )

• average height of a hypertrophic chondrocyte is only about 70% of the controls

delayed endochondral bone ossification ( J:66913 )

• delay in development of diaphyseal and epiphyseal secondary ossification centers by more than 5 days

Genotype
MGI:3688508

hm4

• Allelic Composition: Igf1^tm1Arge/Igf1^tm1Arge
• Genetic Background: involves: 129S/SvEv * MF1

mortality/aging

postnatal lethality, incomplete penetrance ( J:82113 , J:105536 )

• more mice die during the postnatal period than expected (J:82113)

• most homozygotes fail to survive into adulthood (J:105536)

• more than 80% of homozygotes die prior to P30 (J:105536)

hearing/vestibular/ear

delayed inner ear development ( J:71687 )

• at P20, homozygotes display delayed cochlear development at the level of tectorial membrane maturation

abnormal cochlea morphology ( J:71687 )

• at P20, mutant cochleas are grossly normal but significantly smaller than wild-type

• reduction of cochlear volume is nonsignificant (9%) at P5 but quite significant (34%) at P20, and appears later than whole body dwarfism

abnormal tectorial membrane morphology ( J:71687 )

• at P20, an immature tectorial membrane remains physically attached to the underlying ogan of Corti, by a membrane-like remnant of marginal pillars

abnormal otic capsule morphology ( J:71687 )

• at P5, homozygotes display a thicker cartilaginous otic capsule

abnormal auditory brainstem response waveform shape ( J:105536 )

• ABR wave latencies show delayed transmission in the central auditory pathway

• at 90 dB SPL, homozygotes exhibit increased click-ABR latencies for peaks I-IV; interpeak latencies are also increased

• increase in the absolute latency is progressive from peak I to peak IV, indicating a delayed ABR response to acoustic stimuli that increases along the auditory pathway from the periphery to the brainstem level

increased or absent threshold for auditory brainstem response ( J:105536 )

• at 1 month of age, homozygotes exhibit a click-ABR threshold of 75.4 5.4 dB SPL, i.e. a 28 dB SPL threshold elevation relative to heterozygous or wild-type mice

sensorineural hearing loss ( J:105536 )

• at 1 month of age, homozygotes exhibit an all-frequency involved bilateral sensorineural hearing loss

syndromic hearing loss ( J:105536 )

nervous system

increased neuron apoptosis ( J:71687 )

• from P5 to P20, homozygotes exhibit a significant loss of cochlear ganglion neurons due to apoptosis, accompanied by an increased number of neurons expressing activated caspase-3

• apoptosis is more prominent in cells of the basal turn of the cochlea

abnormal olfactory bulb layer morphology ( J:82113 )

• the boundaries between the glomerular layer, the remaining mitral cell layer, and the granule cell layer are diffuse unlike in wild-type mice

abnormal olfactory bulb external plexiform layer morphology ( J:82113 )

• thin

abnormal olfactory bulb mitral cell layer morphology ( J:82113 )

• at E18.5, the mitral cell layer is reduced and disorganized compared to in wild-type mice

abnormal mitral cell morphology ( J:82113 )

• the number of mitral neurons is decreased compared to in wild-type mice

abnormal sensory neuron innervation pattern ( J:71687 )

• homozygotes display abnormal innervation of the sensory cells in the organ of Corti

• at P20, homozygotes maintain innervation to cochlear sensory cells, but their synapses are altered

abnormal cochlear ganglion morphology ( J:71687 )

• homozygotes show a general delay in differentiation of cochlear ganglion cells during postnatal development

• cochlear ganglion fibers display reduced myelination, abnormal synaptogenesis, and deficient innervation of the sensory cells in the organ of Corti

cochlear ganglion degeneration ( J:71687 )

• at P20, homozygotes significant apoptotic cell death in the cochlear ganglion, esp. in the basal turns of the cochlea

small cochlear ganglion ( J:71687 )

• at P20 (but not P5), mutant cochlear ganglia display a 27% reduction in ganglion volume, a 22% reduction in neuron number, and a 31% reduction in neuronal cell volume relative to wild-type

• at P20, homozygotes show loss of large ganglion neurons (>800 m³) which represent 10% of ganglion neurons in wild-type mice

• 75% of mutant ganglion neurons are smaller than 400 m³ vs only 45% in wild-type mice

abnormal cochlear nerve morphology ( J:71687 )

• at P5, all homozygotes show a dispersion of the fibers in the auditory branch of the eighth cranial nerve

• at P20, the cochlear nerve shows a dispersed fiber phenotype in the center of the cochlea, along with reduced neurofilament protein expression in nerve fibers

abnormal myelination ( J:71687 )

• homozygotes exhibit delayed or altered myelination of cochlear ganglia sensory neurons, with a drastic reduction of myelin P0 levels at P20

growth/size/body

decreased body weight ( J:71687 , J:82113 )

• the body weight of homozygotes is reduced between 50% (at P5) and 60% (at P20) relative to that of wild-type littermates (J:71687)

disproportionate dwarf ( J:71687 )

postnatal growth retardation ( J:71687 )

• homozygotes exhibit a general postnatal growth retardation

muscle

muscle hypoplasia ( J:82113 )

respiratory system

abnormal lung morphology ( J:82113 )

• mice exhibit intermediate lung abnormalities compared with wild-type mice and Igf1^tm1Arge Lif^tm1Stw double homozygotes

increased type II pneumocyte number ( J:82113 )

• more PAS+ type 2 cells are detected than in wild-type lungs

skeleton

abnormal skeleton morphology ( J:82113 )

• mice exhibit reduced skeleton size compared with wild-type mice

delayed bone ossification ( J:82113 )

• in the vertebral column, sternae, and xyphoid process of some mice

integument

abnormal hair follicle development ( J:82113 )

• hair eruption is delayed compared to in wild-type mice

cellular

increased neuron apoptosis ( J:71687 )

• from P5 to P20, homozygotes exhibit a significant loss of cochlear ganglion neurons due to apoptosis, accompanied by an increased number of neurons expressing activated caspase-3

• apoptosis is more prominent in cells of the basal turn of the cochlea

Genotype
MGI:3696122

ht5

• Allelic Composition: Igf1^tm1Arge/Igf1⁺
• Genetic Background: involves: 129S/SvEv * MF1

nervous system

small cochlear ganglion ( J:71687 )

• at P20 (but not P5), heterozygotes display a moderate reduction in cochlear ganglion volume (10%) and in neuronal size (12%) relative to wild-type mice

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:105536 )

N • at 3 months, heterozygotes display no significant differences in click-ABR thresholds and interpeak I-IV latencies relative to wild-type mice

Genotype
MGI:3629674

cx6

• Allelic Composition: Igf1^tm1Arge/Igf1^tm1Arge; Igf1r^tm1Arge/Igf1r^tm1Arge
• Genetic Background: either: (involves: 129S/SvEv) or (involves: 129S/SvEv * C57BL/6J) or (involves: 129S/SvEv * MF1)

mortality/aging

neonatal lethality, complete penetrance ( J:15108 )

• die immediately after birth of respiratory failure

growth/size/body

decreased birth weight ( J:15108 )

• birth weight is about 45% of wild-type

respiratory system

respiratory failure ( J:15108 )

skeleton

delayed bone ossification ( J:15108 )

Genotype
MGI:3629689

cx7

• Allelic Composition: Igf1^tm1Arge/Igf1^tm1Arge; Igf2^tm1Rob/Igf2⁺
• Genetic Background: either: (involves: 129S/SvEv) or (involves: 129S/SvEv * C57BL/6J) or (involves: 129S/SvEv * MF1)

mortality/aging

neonatal lethality, complete penetrance ( J:15108 )

• double mutants with a paternally inherited Igf2 allele die shortly after birth of respiratory failure

growth/size/body

decreased birth weight ( J:15108 )

• birth weight is about 30% of wild-type in double mutants with a paternally inherited Igf2 allele

respiratory system

respiratory failure ( J:15108 )

skeleton

delayed bone ossification ( J:15108 )

• double mutants with a paternally inherited Igf2 allele exhibit the same developmental delays in the ossification of particular bones as the Igf1r^tm1Arge single mutants

cellular

maternal imprinting ( J:15108 )

• defects are seen in double mutants with a paternally inherited Igf2 allele

integument

thin epidermis stratum spinosum ( J:15108 )

• the stratum spinosum is underdeveloped in double mutants with a paternally inherited Igf2 allele

Genotype
MGI:4834804

cx8

• Allelic Composition: Igf1^tm1Arge/Igf1⁺; Lif^tm1Stw/Lif^tm1Stw
• Genetic Background: involves: 129S/SvEv * 129S1/Sv

nervous system

decreased motor neuron number ( J:103711 )

• fewer motor neurons are present in the trigeminal nuclei compared to in wild-type mice

Genotype
MGI:4834806

cx9

• Allelic Composition: Igf1^tm1Arge/Igf1^tm1Arge; Lif^tm1Stw/Lif^tm1Stw
• Genetic Background: involves: 129S/SvEv * 129S1/Sv

nervous system

abnormal cerebellar Purkinje cell layer ( J:103711 )

• slightly thinner than normal in some mice

decreased motor neuron number ( J:103711 )

• at E18.5, mice exhibit reduced motor neurons in the brainstem nuclei (trigeminal and facial nuclei) compared with wild-type mice and Igf1^tm1Arge homozygotes

Genotype
MGI:4834783

cx10

• Allelic Composition: Igf1^tm1Arge/Igf1⁺; Lif^tm1Stw/Lif^tm1Stw
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * BALB/c * C57BL/6J * MF1

mortality/aging

postnatal lethality ( J:82113 )

• more mice die during the postnatal period than expected

Genotype
MGI:4834785

cx11

• Allelic Composition: Igf1^tm1Arge/Igf1^tm1Arge; Lif^tm1Stw/Lif⁺
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * BALB/c * C57BL/6J * MF1

mortality/aging

postnatal lethality ( J:82113 )

• more mice die during the postnatal period than expected

skeleton

delayed bone ossification ( J:82113 )

• in some mice

Genotype
MGI:4834786

cx12

• Allelic Composition: Igf1^tm1Arge/Igf1^tm1Arge; Lif^tm1Stw/Lif^tm1Stw
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * BALB/c * C57BL/6J * MF1

mortality/aging

neonatal lethality, complete penetrance ( J:82113 )

• all mice die at birth

nervous system

abnormal olfactory bulb layer morphology ( J:82113 )

• the boundaries between the glomerular layer, the remaining mitral cell layer, and the granule cell layer are diffuse unlike in wild-type mice

abnormal olfactory bulb external plexiform layer morphology ( J:82113 )

• thin

abnormal olfactory bulb mitral cell layer morphology ( J:82113 )

• at E18.5, the mitral cell layer is reduced and disorganized compared to in wild-type mice

abnormal mitral cell morphology ( J:82113 )

• the number of mitral neurons is decreased compared to in wild-type mice

respiratory system

abnormal lung morphology ( J:82113 )

• lung tissue is more compact than in wild-type mice

abnormal pulmonary alveolus morphology ( J:82113 )

• alveolar spaces are very small compared to in wild-type mice

• very few capillaries are found around narrow alveolar spaces unlike in wild-type mice

absent type I pneumocytes ( J:82113 )

• lungs lack flat putative type I cells

abnormal type II pneumocyte morphology ( J:82113 )

• rounded type II cells exhibit microvilli and cytoplasmic extensions unlike alveoli cells in wild-type mice

increased type II pneumocyte number ( J:82113 )

• more PAS+ type II cells are detected than in wild-type lungs

atelectasis ( J:82113 )

thick pulmonary interalveolar septum ( J:82113 )

skeleton

abnormal skeleton morphology ( J:82113 )

• mice exhibit reduced skeleton size compared with wild-type mice and single homozygotes

abnormal long bone morphology ( J:82113 )

• long bones contain abnormal cells unlike in wild-type mice

decreased bone mineral density ( J:82113 )

delayed bone ossification ( J:82113 )

• in the xyphoid process, sternae, ribs, vertebral column, and cranial bones (the nasal, parietal, interparietal and supraoccipital bones)

• impaired ossification is more evident in the skull than in the long bones

fragile skeleton ( J:82113 )

• 3 of 5 skeletons do not survive the staining process

growth/size/body

decreased body size ( J:82113 )

decreased body weight ( J:82113 )

muscle

muscle hypoplasia ( J:82113 )

integument

underdeveloped hair follicles ( J:82113 )

abnormal keratinocyte morphology ( J:82113 )

• keratinocytes in the basal layer are flattened unlike in wild-type mice

thin epidermis ( J:82113 )

Genotype
MGI:3629898

cx13

• Allelic Composition: Gpc3^tm1Arge/Gpc3^tm1Arge; Igf1^tm1Arge/Igf1^tm1Arge
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * C57BL/6J * DBA * MF1

mortality/aging

postnatal lethality, complete penetrance ( J:75054 )

♀ • mutants that are not stillborn die before weaning

perinatal lethality, incomplete penetrance ( J:75054 )

♀ • some mutants are stillborn

Genotype
MGI:3629900

cx14

• Allelic Composition: Gpc3^tm1Arge/Y; Igf1^tm1Arge/Igf1^tm1Arge
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * C57BL/6J * DBA * MF1

mortality/aging

postnatal lethality, complete penetrance ( J:75054 )

♂ • mutants that are not stillborn die before weaning

perinatal lethality, incomplete penetrance ( J:75054 )

♂ • some mutants are stillborn

Genotype
MGI:4834891

cx15

• Allelic Composition: Igf1^tm1Arge/Igf1⁺; Lif^tm1Stw/Lif^tm1Stw
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * C57BL/6 * MF1

growth/size/body

decreased body mass index ( J:87585 )

• female mice exhibit a lower BMI than wild-type mice

decreased body weight ( J:87585 )

• male and female mice weight less than wild type mice

• female mice weigh less than Lif^tm1Stw homozygotes

slow postnatal weight gain ( J:87585 )

• weight gain in female mice arrests at 6 weeks unlike in wild-type mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:87585 )

N • unlike Lif^tm1Stw homozygotes, female mice exhibit normal circulating triglyceride levels

increased circulating insulin-like growth factor I level ( J:87585 )

increased circulating leptin level ( J:87585 )

• more so in female than male mice

increased growth hormone level ( J:87585 )

• slightly in the pituitary

adipose tissue

abnormal white fat cell morphology ( J:87585 )

• in female mice, white adipose tissue cells are depleted of lipid droplets and more compact than in wild-type mice

• in female mice, white adipose tissue cells are replaced with brown adipose tissue cells

decreased gonadal fat pad weight ( J:87585 )

• in female mice

Genotype
MGI:4834892

cx16

• Allelic Composition: Igf1^tm1Arge/Igf1⁺; Lif^tm1Stw/Lif⁺
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * C57BL/6 * MF1

homeostasis/metabolism

increased growth hormone level ( J:87585 )

• slightly in the pituitary

Genotype
MGI:4456249

cx17

• Allelic Composition: Ghr^tm1Arge/Ghr^tm1Arge; Igf1^tm1Arge/Igf1^tm1Arge
• Genetic Background: involves: 129S/SvEv * C57BL/6J * DBA * MF1

growth/size/body

proportional dwarf ( J:66913 )

• double mutants are smaller than either single mutant mouse

postnatal growth retardation ( J:66913 )

• weight at birth and P10 is normal, however after 2 weeks post birth, mice are growth retarded

skeleton

abnormal long bone epiphyseal plate proliferative zone ( J:66913 )

• proliferative zone of chondrocytes is shorter at p22 and p30

• chondrocytes proliferation in the proliferative zone is 43% of wild-type

abnormal long bone hypertrophic chondrocyte zone ( J:66913 )

• reduction in the rate of production and maturation of hypertrophic zone chondrocytes

decreased width of hypertrophic chondrocyte zone ( J:66913 )

• hypertrophic zone of chondrocytes is shorter at p22 and p30

abnormal trabecular bone morphology ( J:66913 )

• reduction in the height of the primary spongiosa

abnormal chondrocyte morphology ( J:66913 )

• average height of a hypertrophic chondrocyte is only about 70% of the controls

delayed endochondral bone ossification ( J:66913 )

• delay in development of diaphyseal and epiphyseal secondary ossification centers due to hypoproliferation and reduced size of hypertrophic chondrocytes