Phenotypes associated with this allele

• Allele Symbol: Fgfr1^tm1Upir
• Allele Name: targeted mutation 1, Ulla Pirvola
• Allele ID: MGI:3528437
• Summary: 11 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Fgfr1^tm1Upir/Fgfr1^tm1.1Upir	involves: C57BL/6J	MGI:3529288
cn2	Cpa3^tm3(icre)Hrr/Cpa3^+ Fgfr1^tm1Upir/Fgfr1^tm1Upir Fgfr2^tm1Dor/Fgfr2^tm1Dor Tg(KRT5-cre)5132Jlj/0	involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * C57BL/6J * DBA/2J	MGI:5642134
cn3	Fgfr1^tm1Upir/Fgfr1^tm1Upir Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * ICR	MGI:3702999
cn4	Fgfr1^tm1Upir/Fgfr1^tm1.1Upir Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * ICR	MGI:3702998
cn5	Fgfr1^tm1Upir/Fgfr1^tm1Upir Fgfr2^tm1Dor/Fgfr2^tm1Dor Gt(ROSA)26Sor^tm1(Cdkn1b,EGFP)Dor/Gt(ROSA)26Sor^+ Myl2^tm1(cre)Krc/Myl2^+	involves: 129/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6	MGI:3775280
cn6	Fgfr1^tm1Upir/Fgfr1^tm1Upir Fgfr2^tm1Dor/Fgfr2^tm1Dor Tg(KRT5-cre)5132Jlj/0	involves: 129X1/SvJ * C57BL/6 * C57BL/6J * DBA/2J	MGI:5642117
cn7	Fgfr1^tm1Upir/Fgfr1^tm1Upir Fgfr2^tm1Dor/Fgfr2^tm1Dor Tg(GFAP-cre)25Mes/0	involves: 129X1/SvJ * FVB/N	MGI:3641106
cn8	Fgfr1^tm1Upir/Fgfr1^tm1Upir Tg(KRT5-cre)5132Jlj/0	involves: C57BL/6 * C57BL/6J * DBA/2J	MGI:5642114
cn9	Fgfr1^tm1Upir/Fgfr1^tm1Upir Tg(Nes-cre)1Kln/0	involves: C57BL/6 * SJL	MGI:3641104
cn10	Fgfr1^tm1Upir/Fgfr1^tm1Upir Tg(GFAP-cre)25Mes/0	involves: FVB/N	MGI:3641103
cn11	Fgfr1^tm1Upir/Fgfr1^tm1Upir Tg(Mnx1-GFP)1Slp/? Tg(Nes-cre)1Kln/?	Not Specified	MGI:3767836

Genotype
MGI:3529288

cn1

• Allelic Composition: Fgfr1^tm1Upir/Fgfr1^tm1.1Upir
• Genetic Background: involves: C57BL/6J

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

cardiovascular system

abnormal myocardial fiber morphology ( J:95803 )

• the thickness of each band of cardiac actin is increased and average sarcomere thickness is increased to 1.01 um compared to 0.65 um in wild-type

thin myocardium ( J:95803 )

• at E12.5 the ventricular wall is thinner than normal

abnormal heart development ( J:95803 )

• individual cardiomyoblasts appear larger and premature differentiation of cardiomyoblasts is seen

increased heart atrium size ( J:95803 )

• at E12.5 the atria are enlarged

heart hypoplasia ( J:95803 )

• severe hypoplasia is seen, however the patterning of the cardiac cushions, septum, and ventricular layers appears normal

• at E12.5 the heart does not fill the pericardial space

• hypoplasia is more severe and uniform than in Fgf9^tm1Dor homozygotes

dilated heart left ventricle ( J:95803 )

• biventricular dilation is seen in newborn mutants

dilated heart right ventricle ( J:95803 )

• biventricular dilation is seen in newborn mutants

abnormal fetal cardiomyocyte proliferation ( J:95803 )

• myocardial proliferation is decreased throughout the base and apex of both ventricles

muscle

abnormal myocardial fiber morphology ( J:95803 )

• the thickness of each band of cardiac actin is increased and average sarcomere thickness is increased to 1.01 um compared to 0.65 um in wild-type

thin myocardium ( J:95803 )

• at E12.5 the ventricular wall is thinner than normal

abnormal fetal cardiomyocyte proliferation ( J:95803 )

• myocardial proliferation is decreased throughout the base and apex of both ventricles

cellular

abnormal fetal cardiomyocyte proliferation ( J:95803 )

• myocardial proliferation is decreased throughout the base and apex of both ventricles

Genotype
MGI:5642134

cn2

• Allelic Composition: Cpa3^tm3(icre)Hrr/Cpa3⁺; Fgfr1^tm1Upir/Fgfr1^tm1Upir; Fgfr2^tm1Dor/Fgfr2^tm1Dor; Tg(KRT5-cre)5132Jlj/0
• Genetic Background: involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * C57BL/6J * DBA/2J

growth/size/body

decreased body weight ( J:221184 )

integument

increased keratinocyte proliferation ( J:221184 )

impaired skin barrier function ( J:221184 )

• increase in transepidermal water loss, indicating an epidermal barrier defect

skin inflammation ( J:221184 )

progressive hair loss ( J:221184 )

acanthosis ( J:221184 )

hematopoietic system

absent mast cells ( J:221184 )

homeostasis/metabolism

impaired skin barrier function ( J:221184 )

• increase in transepidermal water loss, indicating an epidermal barrier defect

immune system

absent mast cells ( J:221184 )

skin inflammation ( J:221184 )

cellular

increased keratinocyte proliferation ( J:221184 )

reproductive system

female infertility ( J:221184 )

♀ • all females are sterile

reduced male fertility ( J:221184 )

♂ • most males are sterile

Genotype
MGI:3702999

cn3

• Allelic Composition: Fgfr1^tm1Upir/Fgfr1^tm1Upir; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * ICR

mortality/aging

neonatal lethality, complete penetrance ( J:78879 )

• phenotype is stated to be comparable to that of mice that are compound heterozygous for Fgfr1^tm1.1Upir and Fgfr1^tm1Upir and also heterozygous for Foxg1^tm1(cre)Skm; however, no data are presented in J:78879

hearing/vestibular/ear

abnormal cochlear sensory epithelium morphology ( J:78879 )

abnormal organ of Corti morphology ( J:78879 )

Genotype
MGI:3702998

cn4

• Allelic Composition: Fgfr1^tm1Upir/Fgfr1^tm1.1Upir; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * ICR

mortality/aging

neonatal lethality, complete penetrance ( J:78879 )

• mutants die within 24 hrs after birth

hearing/vestibular/ear

abnormal cochlea morphology ( J:78879 )

• at birth, mutant cochleae are frequently slightly shorter than normal

• however, mutant otocysts appear morphologically normal at E10.5 and E11.5

• in addition, initiation of cochlear duct outgrowth from the otocyst is unaffected at E12.5

abnormal cochlear sensory epithelium morphology ( J:78879 )

• at birth, the sensory epithelium of the upper cochlear half is arranged in small sensory patches that mainly consist of IHCs and pillar supporting cells, while the lower cochlear half is less severely affected

• in contrast, the vestibular sensory epithelium remains unchanged

abnormal organ of Corti morphology ( J:78879 )

• at around birth, the organ of Corti is severely disrupted due to impaired production of precursor cells between E12 and E15, as shown by BrdU labeling

abnormal cochlear hair cell development ( J:78879 )

• at E16.5, mutants display no molecular signs of HC specification or differentiation in the gap regions found between sensory patches; OHCs are more severely affected

• at E16.5, the remaining HCs in the sensory patches appear to undergo normal differentiation

• at E18.5, most cochlear sections are devoid of HCs and the greater epithelial ridge is abnormally thin, due to reduced precursor cell proliferation in the ventral wall of the cochlear duct between E12 and E15.5

• apparently, the remaining precursors of the organ of Corti preferentially differentiate into IHCs and pillar cells

• no differences in precursor cell proliferation rate are observed in the dorsal, non-sensory wall of the cochlear duct

decreased cochlear hair cell number ( J:78879 )

• at P0, mutants show a 85% reduction in the total number of differentiating HCs relative to wild-type mice

absent cochlear outer hair cells ( J:78879 )

• at birth, only very low numbers of OHCs are formed, and these are located in lower cochlear half

increased cochlear inner hair cell number ( J:78879 )

• at birth, the small sensory patches found in the upper cochlear half frequently show doublet IHCs instead of a single continuous IHC row

abnormal orientation of inner hair cell stereociliary bundles ( J:78879 )

• at birth, the small sensory patches found in the upper cochlear half frequently show an accumulation of disorientated IHCs at the edges

absent organ of Corti supporting cells ( J:78879 )

• at birth, the sensory patches found in the upper cochlear half frequently show no signs of differentiation of supporting cells

nervous system

abnormal cochlear hair cell development ( J:78879 )

• at E16.5, mutants display no molecular signs of HC specification or differentiation in the gap regions found between sensory patches; OHCs are more severely affected

• at E16.5, the remaining HCs in the sensory patches appear to undergo normal differentiation

• at E18.5, most cochlear sections are devoid of HCs and the greater epithelial ridge is abnormally thin, due to reduced precursor cell proliferation in the ventral wall of the cochlear duct between E12 and E15.5

• apparently, the remaining precursors of the organ of Corti preferentially differentiate into IHCs and pillar cells

• no differences in precursor cell proliferation rate are observed in the dorsal, non-sensory wall of the cochlear duct

decreased cochlear hair cell number ( J:78879 )

• at P0, mutants show a 85% reduction in the total number of differentiating HCs relative to wild-type mice

absent cochlear outer hair cells ( J:78879 )

• at birth, only very low numbers of OHCs are formed, and these are located in lower cochlear half

increased cochlear inner hair cell number ( J:78879 )

• at birth, the small sensory patches found in the upper cochlear half frequently show doublet IHCs instead of a single continuous IHC row

abnormal orientation of inner hair cell stereociliary bundles ( J:78879 )

• at birth, the small sensory patches found in the upper cochlear half frequently show an accumulation of disorientated IHCs at the edges

Genotype
MGI:3775280

cn5

• Allelic Composition: Fgfr1^tm1Upir/Fgfr1^tm1Upir; Fgfr2^tm1Dor/Fgfr2^tm1Dor; Gt(ROSA)26Sor^{tm1(Cdkn1b,EGFP)Dor}/Gt(ROSA)26Sor⁺; Myl2^tm1(cre)Krc/Myl2⁺
• Genetic Background: involves: 129/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6

cardiovascular system

heart hypoplasia ( J:131577 )

• mice exhibit smaller hearts than mice homozygous for null alleles of Fgfr1 and Fgfr2 due to decreased myocardial proliferation

• however, coronary development is normal

thin ventricular wall ( J:131577 )

• mice exhibit thinner ventricular walls than mice homozygous for null alleles of Fgfr1 and Fgfr2

Genotype
MGI:5642117

cn6

• Allelic Composition: Fgfr1^tm1Upir/Fgfr1^tm1Upir; Fgfr2^tm1Dor/Fgfr2^tm1Dor; Tg(KRT5-cre)5132Jlj/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * C57BL/6J * DBA/2J

growth/size/body

decreased body size ( J:158802 )

decreased body weight ( J:221184 )

integument

increased keratinocyte proliferation ( J:158802 , J:221184 )

• keratinocyte proliferation is mildly increased at P18 and is strongly increased in the back and tail skin at 3 months of age (J:158802)

• however, keratinocytes in vitro show normal proliferation rate (J:158802)

impaired skin barrier function ( J:158802 , J:221184 )

• transepidermal water loss is slightly increased at P18 and is significantly increased at 6 months of age, indicating disturbed epidermal barrier function (J:158802)

skin inflammation ( J:158802 , J:221184 )

• progressive skin inflammation, with a 60% increase in epidermal gamma-delta T cells, an increase in mast cells in the dermis, and increase in CD45+ alpha-beta and gamma-delta T cells in the dermis (J:158802)

• however, macrophage or neutrophil infiltrate is not seen (J:158802)

dermatitis ( J:221184 )

abnormal skin adnexa morphology ( J:158802 )

• loss of skin appendages

absent sebaceous gland ( J:158802 )

• sebaceous glands are virtually absent in the back skin of older mice

alopecia ( J:158802 )

• mice are hairless by 2-4 months of age

progressive hair loss ( J:158802 , J:221184 )

• progressive hair loss and mice are hairless by 2-4 months of age (J:158802)

abnormal hair follicle morphology ( J:158802 )

• hair follicles are abnormally shaped at P18 (first telogen)

absent hair follicles ( J:158802 )

• hair follicles are virtually absent in the back skin of older mice and only a few cysts are present in the dermis

small hair follicles ( J:158802 )

• hair follicles are smaller at P18 (first telogen), but numbers are normal

abnormal hair cycle ( J:158802 )

• by P30, most follicles are in telogen compared to controls which have entered the second anagen

abnormal epidermal layer morphology ( J:158802 )

• a mild hypotrophy of the epidermis is seen at P5 (first anagen), but the dermis and appendages appear normal

• mice show only a rudimentary development of tight junctions in the epidermis

abnormal epidermis stratum granulosum morphology ( J:158802 )

• bubble-like intercellular clefts between the keratinocytes of the stratum granulosum

acanthosis ( J:158802 , J:221184 )

• mice develop epidermal hyperthickening combined with disorganization of the keratinocytes at 2-3 months of age which progresses with age (J:158802)

thick epidermis ( J:221184 )

abnormal skin appearance ( J:158802 )

• fragile appearing skin

dry skin ( J:158802 )

skin fibrosis ( J:158802 )

• fibrosis develops in the dermis

endocrine/exocrine glands

absent sebaceous gland ( J:158802 )

• sebaceous glands are virtually absent in the back skin of older mice

cellular

increased keratinocyte proliferation ( J:158802 , J:221184 )

• keratinocyte proliferation is mildly increased at P18 and is strongly increased in the back and tail skin at 3 months of age (J:158802)

• however, keratinocytes in vitro show normal proliferation rate (J:158802)

hematopoietic system

abnormal mast cell morphology ( J:221184 )

• mast cells in young cells are degranulated, followed by a decrease in degranulated mast cells thereafter

increased mast cell number ( J:221184 )

• increase in mast cell number between P7 and P9 is greater in mutants than in controls and remains high unlike in controls which show a decrease over time

• higher number of mast cell progenitors in the white adipose tissue

increased IgE level ( J:158802 )

• mice show enhanced levels of IgE in the dermis and in the serum

increased IgG1 level ( J:158802 )

• mice show enhanced levels of IgG1 in the dermis

increased IgG2a level ( J:158802 )

• mice show enhanced levels of IgG2a in the dermis

homeostasis/metabolism

impaired skin barrier function ( J:158802 , J:221184 )

• transepidermal water loss is slightly increased at P18 and is significantly increased at 6 months of age, indicating disturbed epidermal barrier function (J:158802)

abnormal chemokine level ( J:221184 )

• transient increase in mast cell chemokines in the epidermis and dermis

immune system

abnormal mast cell morphology ( J:221184 )

• mast cells in young cells are degranulated, followed by a decrease in degranulated mast cells thereafter

increased mast cell number ( J:221184 )

• increase in mast cell number between P7 and P9 is greater in mutants than in controls and remains high unlike in controls which show a decrease over time

• higher number of mast cell progenitors in the white adipose tissue

increased IgE level ( J:158802 )

• mice show enhanced levels of IgE in the dermis and in the serum

increased IgG1 level ( J:158802 )

• mice show enhanced levels of IgG1 in the dermis

increased IgG2a level ( J:158802 )

• mice show enhanced levels of IgG2a in the dermis

abnormal chemokine level ( J:221184 )

• transient increase in mast cell chemokines in the epidermis and dermis

skin inflammation ( J:158802 , J:221184 )

• progressive skin inflammation, with a 60% increase in epidermal gamma-delta T cells, an increase in mast cells in the dermis, and increase in CD45+ alpha-beta and gamma-delta T cells in the dermis (J:158802)

• however, macrophage or neutrophil infiltrate is not seen (J:158802)

dermatitis ( J:221184 )

behavior/neurological

polydipsia ( J:158802 )

• high consumption of drinking water

reproductive system

female infertility ( J:158802 , J:221184 )

♀ • all females are infertile (J:158802)

reduced male fertility ( J:158802 , J:221184 )

♂ • about 60% of males are infertile (J:158802)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
atopic dermatitis		DOID:3310	OMIM:603165 OMIM:PS603165	J:221184

Genotype
MGI:3641106

cn7

• Allelic Composition: Fgfr1^tm1Upir/Fgfr1^tm1Upir; Fgfr2^tm1Dor/Fgfr2^tm1Dor; Tg(GFAP-cre)25Mes/0
• Genetic Background: involves: 129X1/SvJ * FVB/N

nervous system

abnormal astrocyte morphology ( J:110263 )

• numbers of astrocytes reaching the cortex is significantly reduced compared to controls at P7

Genotype
MGI:5642114

cn8

• Allelic Composition: Fgfr1^tm1Upir/Fgfr1^tm1Upir; Tg(KRT5-cre)5132Jlj/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * DBA/2J

normal phenotype

no abnormal phenotype detected ( J:158802 )

• no obvious abnormalities are seen at any stage of postnatal development

Genotype
MGI:3641104

cn9

• Allelic Composition: Fgfr1^tm1Upir/Fgfr1^tm1Upir; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: C57BL/6 * SJL

nervous system

abnormal dorsal telencephalic commissure morphology ( J:110263 )

• mice have defects in the dorsal telencephalic commissures

• all mutants have a complete absence of midline crossing at the most anterior and posterior region

abnormal corpus callosum morphology ( J:110263 )

• about 20% of mice have a small number of callosal fibers in the region above the hippocampal commissure

abnormal frontal lobe morphology ( J:110263 )

• axons are absent in the contralateral cortex or white matter

• the cortical fibers are trapped within Probst bundles

Genotype
MGI:3641103

cn10

• Allelic Composition: Fgfr1^tm1Upir/Fgfr1^tm1Upir; Tg(GFAP-cre)25Mes/0
• Genetic Background: involves: FVB/N

nervous system

abnormal neuronal migration ( J:110263 )

• in mutants, midline cells do not migrate from the ventricular zone to the subpial region of the dorsomedial pallium

abnormal brain commissure morphology ( J:110263 )

• average midline width of the dorsal commissures is markedly smaller compared to controls; anterior and posterior are significantly more affected than the middle

abnormal corpus callosum morphology ( J:110263 )

• in 83% of mice, there is a complete loss of callosal axons from the motor and somatosensory cortex at birth

abnormal hippocampal commissure morphology ( J:110263 )

• there is a loss of hippocampal commissural axons in neonatal mice

abnormal astrocyte morphology ( J:110263 )

• idusium griseum astroglia are absent in the anterior regions of mutants

• processes emerging from the glial wedge and ventricular zone remain attached at the ventricular zone and the pia and very few astrocytes are observed in between the glial wedge and the idusium griseum

• numbers of astrocytes reaching the cortex are significantly reduced compared to controls

cellular

abnormal neuronal migration ( J:110263 )

• in mutants, midline cells do not migrate from the ventricular zone to the subpial region of the dorsomedial pallium

Genotype
MGI:3767836

cn11

• Allelic Composition: Fgfr1^tm1Upir/Fgfr1^tm1Upir; Tg(Mnx1-GFP)1Slp/?; Tg(Nes-cre)1Kln/?
• Genetic Background: Not Specified

nervous system

abnormal axon guidance ( J:122940 )

• mice display motor axon guidance defects in the area where medial-class spinal motor neuron axons turn from the spinal nerve towards the dermomyotome

abnormal motor neuron morphology ( J:122940 )

• mice display motor axon guidance defects in the area where medial-class spinal motor neuron axons turn from the spinal nerve towards the dermomyotome

• motor neuron axons are less fasciculated than in heterozygotes

• unlike in wild-type mice, motor neuron axons growth far into the dorsal root ganglia

cellular

abnormal axon guidance ( J:122940 )

• mice display motor axon guidance defects in the area where medial-class spinal motor neuron axons turn from the spinal nerve towards the dermomyotome