Phenotypes associated with this allele

• Allele Symbol: Fgfr2^tm1Dor
• Allele Name: targeted mutation 1, David M Ornitz
• Allele ID: MGI:3044679
• Summary: 34 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Fgfr2^tm1Dor/Fgfr2^svs	involves: 129X1/SvJ * CXB5/ByJ * FVB/N	MGI:3705020
cn2	Fgfr2^tm1Dor/Fgfr2^tm1Dor Fgfr3^tm6.1Cxd/Fgfr3^tm6.1Cxd Foxg1^tm1(cre)Skm/Foxg1^+ Fgfr1^tm3.1Sor/Fgfr1^tm1Jpa Frs3^tm1Jheb/Frs3^tm1Jheb	involves: 129	MGI:6116893
cn3	Fgfr2^tm1Dor/Fgfr2^tm1Dor Fgfr3^tm6.1Cxd/Fgfr3^tm6.1Cxd Foxg1^tm1(cre)Skm/Foxg1^+ Fgfr1^tm1Jpa/Fgfr1^tm1Jpa Frs3^tm1Jheb/Frs3^tm1Jheb	involves: 129	MGI:6116891
cn4	Fgfr2^tm1Dor/Fgfr2^tm1Dor Foxg1^tm1(cre)Skm/Foxg1^+ Fgfr1^tm3.1Sor/Fgfr1^tm1Jpa	involves: 129	MGI:6116896
cn5	Fgfr2^tm1Dor/Fgfr2^tm1Dor Foxg1^tm1(cre)Skm/Foxg1^+ Fgfr1^tm1Jpa/Fgfr1^tm1Jpa	involves: 129	MGI:6116895
cn6	Fgfr2^tm1Dor/Fgfr2^+ Fgfr3^tm6.1Cxd/Fgfr3^tm6.1Cxd Foxg1^tm1(cre)Skm/Foxg1^+ Fgfr1^tm1Jpa/Fgfr1^tm1Jpa Frs3^tm1Jheb/Frs3^tm1Jheb	involves: 129	MGI:6116892
cn7	Fgfr2^tm1Dor/Fgfr2^tm1Dor Fgfr3^tm6.1Cxd/Fgfr3^tm6.1Cxd Foxg1^tm1(cre)Skm/Foxg1^+ Fgfr1^tm6.1Jrt/Fgfr1^tm1Jpa	involves: 129	MGI:6116894
cn8	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
cn9	Fgfr1^tm1Jpa/Fgfr1^tm1Jpa Fgfr2^tm1Dor/Fgfr2^tm1Dor Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129S1/Sv * 129X1/SvJ	MGI:5694226
cn10	Fgfr1^tm1Jpa/Fgfr1^tm1Jpa Fgfr2^tm1Dor/Fgfr2^tm1Dor Twist2^tm1.1(cre)Dor/Twist2^+	involves: 129S1/Sv * 129X1/SvJ	MGI:5694227
cn11	Fgfr2^tm1Dor/Fgfr2^tm1Dor Lamb2^tm1Jrs/Lamb2^tm1Jrs Tg(Mnx1-cre)1Jrs/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3766403
cn12	Fgfr1^tm1Jpa/Fgfr1^tm1.1Jpa Fgfr2^tm1Dor/Fgfr2^tm1.1Dor Twist2^tm1(cre)Dor/Twist2^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3813486
cn13	Fgfr1^tm1Jpa/Fgfr1^tm1Jpa Fgfr2^tm1Dor/Fgfr2^tm1Dor Tg(Msx2-rtTA)888Lma/0 Tg(tetO-cre)1Jaw/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5694225
cn14	Fgfr1^tm1Jpa/Fgfr1^+ Fgfr2^tm1Dor/Fgfr2^tm1.1Dor Twist2^tm1(cre)Dor/Twist2^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3813484
cn15	Fgfr1^tm1Jpa/Fgfr1^tm1.1Jpa Fgfr2^tm1Dor/Fgfr2^+ Twist2^tm1(cre)Dor/Twist2^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3813483
cn16	Fgfr1^tm1Jpa/Fgfr1^tm1Jpa Fgfr2^tm1Dor/Fgfr2^tm1Dor	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J	MGI:3829046
cn17	Fgfr1^tm1Jpa/Fgfr1^tm1Jpa Fgfr2^tm1Dor/Fgfr2^tm1Dor Tg(Pax3-cre)1Joe/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5438672
cn18	Fgfr1^tm1Jpa/Fgfr1^tm1Jpa Fgfr2^tm1Dor/Fgfr2^+ Tg(Pax3-cre)1Joe/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5438670
cn19	Fgfr1^tm1Jpa/Fgfr1^+ Fgfr2^tm1Dor/Fgfr2^tm1Dor Tg(Pax3-cre)1Joe/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5438671
cn20	Fgfr1^tm3.2Cxd/Fgfr1^tm3.2Cxd Fgfr2^tm1Dor/Fgfr2^tm1Dor Foxa2^tm2.1(cre/Esr1*)Moon/Foxa2^+	involves: 129S6/SvEvTac * 129X1/SvJ	MGI:3829047
cn21	Fgfr1^tm1Swnr/Fgfr1^tm1Swnr Fgfr2^tm1Dor/Fgfr2^tm1Dor Tg(KRT5-cre)5132Jlj/0	involves: 129S7/SvEvBrd * 129X1/SvJ * C57BL/6 * C57BL/6J * DBA/2J	MGI:5642123
cn22	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
cn23	Fgfr2^tm1Dor/Fgfr2^tm1.1Dor Twist2^tm1(cre)Dor/Twist2^+	involves: 129X1/SvJ	MGI:3044704
cn24	Fgfr2^tm1Dor/Fgfr2^tm1Dor Tg(Mnx1-cre)1Jrs/?	involves: 129X1/SvJ * C57BL/6	MGI:3766402
cn25	Fgfr1^tm1Upir/Fgfr1^tm1Upir Fgfr2^tm1Dor/Fgfr2^tm1Dor Tg(KRT5-cre)5132Jlj/0	involves: 129X1/SvJ * C57BL/6 * C57BL/6J * DBA/2J	MGI:5642117
cn26	Fgfr2^tm1Dor/Fgfr2^tm1Dor Tg(KRT5-cre)5132Jlj/0	involves: 129X1/SvJ * C57BL/6 * C57BL/6J * DBA/2J	MGI:5642116
cn27	Fgfr2^tm1Dor/Fgfr2^tm1Dor Tg(Sftpc-cre)1Blh/0	involves: 129X1/SvJ * C57BL/6 * DBA/2	MGI:3851800
cn28	Fgfr2^tm1Dor/Fgfr2^tm1Dor H2az2^Tg(Wnt1-cre)11Rth/H2az2^+	involves: 129X1/SvJ * C57BL/6J * CBA/J	MGI:4943276
cn29	Fgfr2^tm1Dor/Fgfr2^tm1Dor Tg(Pax6-cre,GFP)1Pgr/0	involves: 129X1/SvJ * FVB	MGI:4943279
cn30	Fgfr1^tm1Upir/Fgfr1^tm1Upir Fgfr2^tm1Dor/Fgfr2^tm1Dor Tg(GFAP-cre)25Mes/0	involves: 129X1/SvJ * FVB/N	MGI:3641106
cn31	Fgfr2^tm1Dor/Fgfr2^tm1Dor Tg(GFAP-cre)25Mes/0	involves: 129X1/SvJ * FVB/N	MGI:3641105
cn32	Fgfr1^tm1Jpa/Fgfr1^tm1Jpa Fgfr2^tm1Dor/Fgfr2^tm1Dor Tg(Hoxb7-cre)5526Cmb/0	involves: FVB/N	MGI:3525690
cn33	Fgfr1^tm1Jpa/Fgfr1^tm1Jpa Fgfr2^tm1Dor/Fgfr2^+ Tg(Hoxb7-cre)5526Cmb/0	involves: FVB/N	MGI:3525679
cn34	Fgfr1^tm1Jpa/Fgfr1^+ Fgfr2^tm1Dor/Fgfr2^tm1Dor Tg(Hoxb7-cre)5526Cmb/0	involves: FVB/N	MGI:3525687

Genotype
MGI:3705020

ht1

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2^svs
• Genetic Background: involves: 129X1/SvJ * CXB5/ByJ * FVB/N

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

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:119935 )

N • seminal vesicle defects seen in svs/svs mice are complemented by presence of functional Fgfr2 allele

Genotype
MGI:6116893

cn2

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2^tm1Dor; Fgfr3^tm6.1Cxd/Fgfr3^tm6.1Cxd; Foxg1^tm1(cre)Skm/Foxg1⁺; Fgfr1^tm3.1Sor/Fgfr1^tm1Jpa; Frs3^tm1Jheb/Frs3^tm1Jheb
• Genetic Background: involves: 129

cellular

cellular phenotype ( J:242687 )

N • cell division at E8.75 according to mitotic marker p-HH3 immunoreactivity

increased cell death ( J:242687 )

• according to TUNEL assay at E8.75

nervous system

absent telencephalon ( J:242687 )

• at E12.5

Genotype
MGI:6116891

cn3

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2^tm1Dor; Fgfr3^tm6.1Cxd/Fgfr3^tm6.1Cxd; Foxg1^tm1(cre)Skm/Foxg1⁺; Fgfr1^tm1Jpa/Fgfr1^tm1Jpa; Frs3^tm1Jheb/Frs3^tm1Jheb
• Genetic Background: involves: 129

nervous system

absent telencephalon ( J:242687 )

• at E12.5

Genotype
MGI:6116896

cn4

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2^tm1Dor; Foxg1^tm1(cre)Skm/Foxg1⁺; Fgfr1^tm3.1Sor/Fgfr1^tm1Jpa
• Genetic Background: involves: 129

craniofacial

frontonasal prominence hypoplasia ( J:242687 )

• at E12.5

nervous system

telencephalon hypoplasia ( J:242687 )

• reduction in size across A/P and D/V axes at E12.5

abnormal lateral ganglionic eminence morphology ( J:242687 )

• absent at E13.5 according to lack of Lhx8- and Nkx2-1-labeling of LGE region

abnormal medial ganglionic eminence morphology ( J:242687 )

• absent at E13.5 according to lack of Lhx8- and Nkx2-1-labeling of MGE region

vision/eye

microphthalmia ( J:242687 )

• at E12.5

Genotype
MGI:6116895

cn5

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2^tm1Dor; Foxg1^tm1(cre)Skm/Foxg1⁺; Fgfr1^tm1Jpa/Fgfr1^tm1Jpa
• Genetic Background: involves: 129

craniofacial

frontonasal prominence hypoplasia ( J:242687 )

• at E12.5

nervous system

telencephalon hypoplasia ( J:242687 )

• reduction in size across A/P and D/V axes at E12.5

vision/eye

microphthalmia ( J:242687 )

• at E12.5

Genotype
MGI:6116892

cn6

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2⁺; Fgfr3^tm6.1Cxd/Fgfr3^tm6.1Cxd; Foxg1^tm1(cre)Skm/Foxg1⁺; Fgfr1^tm1Jpa/Fgfr1^tm1Jpa; Frs3^tm1Jheb/Frs3^tm1Jheb
• Genetic Background: involves: 129

cellular

cellular phenotype ( J:242687 )

N • cell survival and cell division at E8.75 according to mitotic marker p-HH3 immunoreactivity

nervous system

nervous system phenotype ( J:242687 )

N • brain morphology at E12.5

Genotype
MGI:6116894

cn7

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2^tm1Dor; Fgfr3^tm6.1Cxd/Fgfr3^tm6.1Cxd; Foxg1^tm1(cre)Skm/Foxg1⁺; Fgfr1^tm6.1Jrt/Fgfr1^tm1Jpa
• Genetic Background: involves: 129

nervous system

nervous system phenotype ( J:242687 )

N • brain morphology at E12.5

Genotype
MGI:5642134

cn8

• 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:5694226

cn9

• Allelic Composition: Fgfr1^tm1Jpa/Fgfr1^tm1Jpa; Fgfr2^tm1Dor/Fgfr2^tm1Dor; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

reproductive system

reproductive system phenotype ( J:223057 )

N • mice exhibit normal early growth, size and shape of genital tubercles

renal/urinary system

abnormal urethra urothelium morphology ( J:223057 )

• abnormal maturation of urethral epithelium

Genotype
MGI:5694227

cn10

• Allelic Composition: Fgfr1^tm1Jpa/Fgfr1^tm1Jpa; Fgfr2^tm1Dor/Fgfr2^tm1Dor; Twist2^{tm1.1(cre)Dor}/Twist2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

reproductive system

genital tubercle hypoplasia ( J:223057 )

• small

abnormal reproductive system physiology ( J:223057 )

• reduced cell proliferation in genital mesenchyme

Genotype
MGI:3766403

cn11

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2^tm1Dor; Lamb2^tm1Jrs/Lamb2^tm1Jrs; Tg(Mnx1-cre)1Jrs/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

nervous system

abnormal synaptic vesicle clustering ( J:126496 )

• at P14, vesicles were highly clustered at synaptic site, but were abundant in preterminal portions

Genotype
MGI:3813486

cn12

• Allelic Composition: Fgfr1^tm1Jpa/Fgfr1^tm1.1Jpa; Fgfr2^tm1Dor/Fgfr2^tm1.1Dor; Twist2^tm1(cre)Dor/Twist2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

digestive/alimentary system

abnormal small intestine morphology ( J:139005 )

• there is about a third reduction in the length of the small intestine at E18.5 compared to controls

abnormal small intestine crypts of Lieberkuhn morphology ( J:139005 )

• premature crypt-like structures occur in the small intestine of E18.5 embryos before the appearance of paneth cells

abnormal digestive system physiology ( J:139005 )

• proliferation of fibroblasts found in the proximal and distal small intestine mesenchyme is significantly reduced at E18.5

endocrine/exocrine glands

abnormal small intestine crypts of Lieberkuhn morphology ( J:139005 )

• premature crypt-like structures occur in the small intestine of E18.5 embryos before the appearance of paneth cells

Genotype
MGI:5694225

cn13

• Allelic Composition: Fgfr1^tm1Jpa/Fgfr1^tm1Jpa; Fgfr2^tm1Dor/Fgfr2^tm1Dor; Tg(Msx2-rtTA)888Lma/0; Tg(tetO-cre)1Jaw/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

reproductive system

genital tubercle hypoplasia ( J:223057 )

• underdeveloped from E11.5

• deficiency in proximodistal outgrowth at E12.5

• smaller in size at E15.5 with a lack in mesenchymal patterning

abnormal reproductive system physiology ( J:223057 )

• at E11.0, genital mesenchyme exhibits a reduction in cell proliferation compared with in wild-type mice

• however, apoptosis rates are normal

Genotype
MGI:3813484

cn14

• Allelic Composition: Fgfr1^tm1Jpa/Fgfr1⁺; Fgfr2^tm1Dor/Fgfr2^tm1.1Dor; Twist2^tm1(cre)Dor/Twist2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

digestive/alimentary system

abnormal small intestine morphology ( J:139005 )

• there is about a 15% reduction in the length of the small intestine at E18.5 compared to controls

Genotype
MGI:3813483

cn15

• Allelic Composition: Fgfr1^tm1Jpa/Fgfr1^tm1.1Jpa; Fgfr2^tm1Dor/Fgfr2⁺; Twist2^tm1(cre)Dor/Twist2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

digestive/alimentary system

abnormal small intestine morphology ( J:139005 )

• there is about a 15% reduction in the length of the small intestine at E18.5 compared to controls

Genotype
MGI:3829046

cn16

• Allelic Composition: Fgfr1^tm1Jpa/Fgfr1^tm1Jpa; Fgfr2^tm1Dor/Fgfr2^tm1Dor
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J

craniofacial

facial cleft ( J:143444 )

• severe facial clefting is seen

cardiovascular system

cardiovascular system phenotype ( J:143444 )

N • despite ubiquitous expression of these genes in the anterior of the embryo, no defects in outflow tract development are seen

growth/size/body

facial cleft ( J:143444 )

• severe facial clefting is seen

Genotype
MGI:5438672

cn17

• Allelic Composition: Fgfr1^tm1Jpa/Fgfr1^tm1Jpa; Fgfr2^tm1Dor/Fgfr2^tm1Dor; Tg(Pax3-cre)1Joe/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

renal/urinary system

increased metanephric mesenchyme apoptosis ( J:107078 )

• at E10.5, many apoptotic (TUNEL+) cells are present in the very loose mesenchyme adjacent to the ureteric bud, unlike in controls

increased kidney apoptosis ( J:107078 )

• abnormally high rates of apoptosis are detected in mesenchyme dorsal to the initial ureteric bud at E10.5 and then in the rudimentary ureteric bud and Wolffian duct at E11.5

decreased kidney cell proliferation ( J:107078 )

• at E10.5, mice exhibit local areas of hypoproliferation (decreased BrdU uptake) in mesenchyme dorsal to the ureteric bud (where metanephric mesenchyme should be present)

absent metanephric mesenchyme ( J:107078 )

• at E10.5, mice exhibit no histologically recognizable condensing metanephric mesenchyme within the loose mesenchyme, unlike controls

• by E11.5, no definitive metanephric mesenchyme is seen around the unbranched ureteric buds, unlike in controls

absent kidney ( J:107078 )

• mice exhibit total renal aplasia

• however, mice develop bladders and structures originating from intermediate mesoderm including ovaries, testes, Mullerian ducts, and ductus deferens

abnormal ureteric bud morphology ( J:107078 )

• mice occasionally develop two initial ureteric buds from the Wolffian duct, unlike controls

impaired branching involved in ureteric bud morphogenesis ( J:107078 )

• failure of uteretic buds to branch by E11.5

abnormal ureteric bud elongation ( J:107078 )

• by E11.5, ureteric buds fail to elongate or branch

ectopic ureteric bud ( J:107078 )

• mice occasionally develop an ectopic ureteric bud

small ureteric bud ( J:107078 )

• a smaller ureteric bud is usually observed at E10.5 and E11.0

cellular

increased metanephric mesenchyme apoptosis ( J:107078 )

• at E10.5, many apoptotic (TUNEL+) cells are present in the very loose mesenchyme adjacent to the ureteric bud, unlike in controls

increased kidney apoptosis ( J:107078 )

• abnormally high rates of apoptosis are detected in mesenchyme dorsal to the initial ureteric bud at E10.5 and then in the rudimentary ureteric bud and Wolffian duct at E11.5

decreased kidney cell proliferation ( J:107078 )

• at E10.5, mice exhibit local areas of hypoproliferation (decreased BrdU uptake) in mesenchyme dorsal to the ureteric bud (where metanephric mesenchyme should be present)

embryo

increased metanephric mesenchyme apoptosis ( J:107078 )

• at E10.5, many apoptotic (TUNEL+) cells are present in the very loose mesenchyme adjacent to the ureteric bud, unlike in controls

Genotype
MGI:5438670

cn18

• Allelic Composition: Fgfr1^tm1Jpa/Fgfr1^tm1Jpa; Fgfr2^tm1Dor/Fgfr2⁺; Tg(Pax3-cre)1Joe/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

renal/urinary system

renal/urinary system phenotype ( J:107078 )

N • mice exhibit normal-appearing kidneys after birth

N • kidneys exhibit normal cortical and medullary structures at E16.5 and remain normal throughout embryonic development

Genotype
MGI:5438671

cn19

• Allelic Composition: Fgfr1^tm1Jpa/Fgfr1⁺; Fgfr2^tm1Dor/Fgfr2^tm1Dor; Tg(Pax3-cre)1Joe/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

renal/urinary system

renal/urinary system phenotype ( J:107078 )

N • mice exhibit normal-appearing kidneys after birth

N • kidneys exhibit normal cortical and medullary structures at E16.5 and remain normal throughout embryonic development

Genotype
MGI:3829047

cn20

• Allelic Composition: Fgfr1^tm3.2Cxd/Fgfr1^tm3.2Cxd; Fgfr2^tm1Dor/Fgfr2^tm1Dor; Foxa2^{tm2.1(cre/Esr1*)Moon}/Foxa2⁺
• Genetic Background: involves: 129S6/SvEvTac * 129X1/SvJ

mortality/aging

mortality/aging ( J:143444 )

N • despite disruption of vascular development mice survive to birth

cardiovascular system

cardiovascular system phenotype ( J:143444 )

N • despite ubiquitous expression of these genes in the anterior of the embryo, no defects in outflow tract development are seen

abnormal vascular development ( J:143444 )

• disruption of vascular development

Genotype
MGI:5642123

cn21

• Allelic Composition: Fgfr1^tm1Swnr/Fgfr1^tm1Swnr; Fgfr2^tm1Dor/Fgfr2^tm1Dor; Tg(KRT5-cre)5132Jlj/0
• Genetic Background: involves: 129S7/SvEvBrd * 129X1/SvJ * C57BL/6 * C57BL/6J * DBA/2J

growth/size/body

decreased body size ( J:158802 )

integument

abnormal skin adnexa morphology ( J:158802 )

• progressive loss of skin appendages

progressive hair loss ( J:158802 )

• progressive hair loss such that mice are hairless by 1 month of age

acanthosis ( J:158802 )

• mice develop epidermal hyperthickening combined with disorganization of the keratinocytes which progresses with age

Genotype
MGI:3775280

cn22

• 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:3044704

cn23

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2^tm1.1Dor; Twist2^tm1(cre)Dor/Twist2⁺
• Genetic Background: involves: 129X1/SvJ

cellular

abnormal osteoclast differentiation ( J:90391 )

• osteoclasts were more mature (larger) than in control mice, but osteoclast activity did not differ from that of wild-type

decreased cell proliferation ( J:90391 )

• impaired osteoblast proliferation

• no increase in osteoblast apoptosis

abnormal osteoblast physiology ( J:90391 )

• the mineral apposition rate (MAR) was undetectable at 3 and 4 weeks of age

craniofacial

domed cranium ( J:90391 )

growth/size/body

disproportionate dwarf ( J:90391 )

• characterized by reduced bone growth

postnatal growth retardation ( J:90391 )

• mice were 40% to 50% smaller than wild-type controls at 4 weeks of age

• normal growth resumed but adult mice remained 30% to 40% smaller than wild-type controls

limbs/digits/tail

short femur ( J:90391 )

• reduced length

skeleton

abnormal osteoblast physiology ( J:90391 )

• the mineral apposition rate (MAR) was undetectable at 3 and 4 weeks of age

abnormal appendicular skeleton morphology ( J:90391 )

• shortened appendicular skeleton

short femur ( J:90391 )

• reduced length

abnormal long bone metaphysis morphology ( J:90391 )

• 40% decrease in metaphyseal area due to a reduction in the trabecular zone length and width

abnormal axial skeleton morphology ( J:90391 )

• shortened axial skeleton

domed cranium ( J:90391 )

abnormal vertebrae morphology ( J:90391 )

abnormal thoracic vertebrae morphology ( J:90391 )

abnormal cervical vertebrae morphology ( J:90391 )

abnormal vertebrae development ( J:90391 )

• observed in some mice

• non-ossified gap in the dorsal midline of both the cervical and thoracic vertebrae

absent vertebral spinous process ( J:90391 )

decreased bone mineral density ( J:90391 )

• bone mineral density was reduced in all mice

• though density increased with age, it remained decreased relative to that of wild-type

decreased osteoblast cell number ( J:90391 )

• while osteoblast differentiation was not affected, osteogenic regions contained fewer osteoblasts due to impaired proliferation

abnormal joint morphology ( J:90391 )

• several tarsal joins failed to develop, putatively due to a a failure of cavitation of the cartilaginous anlage prior to ossificiation of these bones

abnormal skeleton development ( J:90391 )

• skeletal dwarfism and decreased bone density

• decreased amount of trabecular bone; in some cases it was absent

abnormal osteoclast differentiation ( J:90391 )

• osteoclasts were more mature (larger) than in control mice, but osteoclast activity did not differ from that of wild-type

abnormal long bone hypertrophic chondrocyte zone ( J:90391 )

• reduced hypertrophic chondrocyte zone

hematopoietic system

abnormal osteoclast differentiation ( J:90391 )

• osteoclasts were more mature (larger) than in control mice, but osteoclast activity did not differ from that of wild-type

immune system

abnormal osteoclast differentiation ( J:90391 )

• osteoclasts were more mature (larger) than in control mice, but osteoclast activity did not differ from that of wild-type

Genotype
MGI:3766402

cn24

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2^tm1Dor; Tg(Mnx1-cre)1Jrs/?
• Genetic Background: involves: 129X1/SvJ * C57BL/6

growth/size/body

decreased body size ( J:126496 )

• smaller than litter mate controls

• born in expected Mendelian numbers

behavior/neurological

tremors ( J:126496 )

• exhibited a mild tremor

nervous system

abnormal synaptic vesicle clustering ( J:126496 )

• at embryonic stages, vesicles were less concentrated at synaptic sites than in controls

• a similar defect was observed in neonates and during the first postnatal week

• the abnormality was transient and barely detectable by the third postnatal week

• neuromuscular junctions formed on schedule

Genotype
MGI:5642117

cn25

• 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:5642116

cn26

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

endocrine/exocrine glands

decreased sebaceous gland number ( J:158802 )

• loss of sebaceous glands

integument

decreased sebaceous gland number ( J:158802 )

• loss of sebaceous glands

abnormal coat/ hair morphology ( J:158802 )

• hair abnormalities

progressive hair loss ( J:158802 )

Genotype
MGI:3851800

cn27

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2^tm1Dor; Tg(Sftpc-cre)1Blh/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * DBA/2

embryo

decreased embryo size ( J:150706 )

• E12.5 embryos are noticeably smaller than controls

growth/size/body

decreased embryo size ( J:150706 )

• E12.5 embryos are noticeably smaller than controls

respiratory system

abnormal lung development ( J:150706 )

• apoptosis is expanded caudally in the bronchial epithelium compared to controls at E11.25

• widespread apoptosis occurs in the lung epithelium by E12.5 and is also observed in the lung mesenchyme

impaired branching involved in bronchus morphogenesis ( J:150706 )

• some E11.5 embryos have smaller lung branches with a bumpy, irregular morphology

• by E12.5, irregular outgrowths have arisen along the entire length of both main bronchi of the mutant lungs with outgrowths concentrated more caudally

• mesenchymal protrusions without an accompanying epithelial branch are occasionally observed during embryonic development

Genotype
MGI:4943276

cn28

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2^tm1Dor; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6J * CBA/J

vision/eye

vision/eye phenotype ( J:130571 )

N • lacrimal gland development is normal

Genotype
MGI:4943279

cn29

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2^tm1Dor; Tg(Pax6-cre,GFP)1Pgr/0
• Genetic Background: involves: 129X1/SvJ * FVB

endocrine/exocrine glands

abnormal lacrimal gland development ( J:130571 )

• at E14.5, the presumptive lacrimal gland precursor remains a thin layer of epithelial cells with little proliferation and no budding unlike in wild-type mice

absent lacrimal gland bud ( J:130571 )

• at E14.5, mutants never develop lacrimal buds

absent lacrimal glands ( J:130571 )

vision/eye

abnormal lacrimal gland development ( J:130571 )

• at E14.5, the presumptive lacrimal gland precursor remains a thin layer of epithelial cells with little proliferation and no budding unlike in wild-type mice

absent lacrimal gland bud ( J:130571 )

• at E14.5, mutants never develop lacrimal buds

absent lacrimal glands ( J:130571 )

Genotype
MGI:3641106

cn30

• 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:3641105

cn31

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

nervous system

abnormal brain morphology ( J:110263 )

• mice show a subtle reduction in cortical size compared to control mice

abnormal astrocyte morphology ( J:110263 )

• numbers of astrocytes reaching the cortex is significantly reduced compared to controls at P7; greatest loss (60%) is in the upper cortical layers with 22% loss in the subcortical white matter

• there is an intermediate reduction (39%) in astrocte density was seen in the inferior cortical layers

Genotype
MGI:3525690

cn32

• Allelic Composition: Fgfr1^tm1Jpa/Fgfr1^tm1Jpa; Fgfr2^tm1Dor/Fgfr2^tm1Dor; Tg(Hoxb7-cre)5526Cmb/0
• Genetic Background: involves: FVB/N

renal/urinary system

decreased renal glomerulus number ( J:95018 )

• reduced numbers of glomeruli in both embryonic and adult kidneys

hydronephrosis ( J:95018 )

• some adult mutants had hydronephrosis occurring unilaterally or bilaterally

small kidney ( J:95018 )

• E13.5 and E16.5 kidneys were smaller than controls

• many adult mutants had small, abnormally shaped kidneys

abnormal ureteric bud morphology ( J:95018 )

• E11.5 ureteric bud explants had abnormally thin, long ureteric stalks and fewer peripheral tips, with a range in phenotype severity

• decrease in the mean number of ureteric bud tips on the surface of E16.5 kidneys

• range of ureteric bud defects at E16.5, including extremely small kidneys with large areas devoid of ureteric tissue

Genotype
MGI:3525679

cn33

• Allelic Composition: Fgfr1^tm1Jpa/Fgfr1^tm1Jpa; Fgfr2^tm1Dor/Fgfr2⁺; Tg(Hoxb7-cre)5526Cmb/0
• Genetic Background: involves: FVB/N

renal/urinary system

renal/urinary system phenotype ( J:95018 )

N • normal kidneys and no apparent renal abnormalities

Genotype
MGI:3525687

cn34

• Allelic Composition: Fgfr1^tm1Jpa/Fgfr1⁺; Fgfr2^tm1Dor/Fgfr2^tm1Dor; Tg(Hoxb7-cre)5526Cmb/0
• Genetic Background: involves: FVB/N

renal/urinary system

decreased renal glomerulus number ( J:95018 )

• 22% and 24% fewer glomeruli in E11.5 explants and adult kidneys, respectively

abnormal kidney development ( J:95018 )

• defects in cortical stromal mesenchyme patterning, showing aberrantly thickened stroma in subcapsular regions in E13.5 kidneys and regions of massive subcapsular apoptosis in stroma

• absent intercalated stripes of stromal cells in E13.5 kidneys

hydronephrosis ( J:95018 )

• 20% of adult mutants had hydronephrosis occurring unilaterally or bilaterally

small kidney ( J:95018 )

• E13.5 and E16.5 kidneys were smaller than controls

• 80% of adult mutants had small, abnormally shaped kidneys

abnormal ureteric bud morphology ( J:95018 )

• range of ureteric bud defects at E16.5, including extremely small kidneys with large areas devoid of ureteric tissue

• increased apoptotic nuclei in ureteric buds (2-3 apoptotic nuclei compared to none or just one in controls)

• decreased rates of proliferation in ureteric bud tips compared with controls

impaired branching involved in ureteric bud morphogenesis ( J:95018 )

• E11.5 ureteric bud explants exhibited aberrant branching and had abnormally thin, long ureteric stalks and fewer peripheral tips, with a range in phenotype severity

• decrease in the mean number of ureteric bud tips on the surface of E16.5 kidneys (89.5 versus 271 in control)