Mouse Genome Informatics
hm1
    Fgf8tm1.3Mrt/Fgf8tm1.3Mrt
involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype


Mouse Genome Informatics
ht2
    Fgf8tm1.2Mrt/Fgf8tm1.3Mrt
involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype


Mouse Genome Informatics
cn3
    Fgf8tm1.3Mrt/Fgf8tm1.3Mrt
Six1tm1(cre,ALPP)Xli/Six1+

involves: 129 * 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• 83% display great vessel defects like cervical aortic arch or interrupted aortic arch type B
• embryos have severely hypoplastic proximal and distal outflow tract cushions compared to wild-type controls


Mouse Genome Informatics
cn4
    Fgf8tm1.3Mrt/Fgf8tm2Mrt
Nkx2-5tm1(cre)Rjs/Nkx2-5+

involves: 129 * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• phenotype is stated to be identical to that of Fgf8tm1.3Mrt/ Fgf8tm1.4Mrt; Nkx2-5tm1(cre)Rjs/ Nkx2-5+ mutants; however no data are presented (J:109474)

embryogenesis
• at E9.5 cell proliferation in pharyngeal endoderm is reduced with cell mitotic indices decreased by 60% relative to controls
• excessive neural crest cell death is observed in pharyngeal arch mesenchyme at E9.5
• thinning of splanchnic mesoderm (SM) layers
• at E9.5 cell proliferation in SM is reduced with cell mitotic indices decreased by 50% relative to controls
• excessive cell death is detected from E8.5-9.5 in SM immediately distal to emerging outflow tract and in endoderm adjacent to the SM
• excessive neural crest cell death is observed in pharyngeal arch mesenchyme at E9.5, as well as in presumptive cardiac neural crest cells in close proximity to outflow tract

cardiovascular system
• phenotype is stated to be identical to that of Fgf8tm1.3Mrt/ Fgf8tm1.4Mrt; Nkx2-5tm1(cre)Rjs/ Nkx2-5+ mutants; however no data are presented
• anterior heart field (AHF) cells are mildly reduced compared to controls, resulting in thinning of splanchnic mesoderm (SM) layers
• at E9.5 cell proliferation in SM is reduced with cell mitotic indices decreased by 50% relative to controls; excessive cell death is detected from E8.5-9.5 in SM immediately distal to emerging outflow tract and in endoderm adjacent to the SM, with excessive cell death expanding into ventral pharyngeal endoderm by E9.5 but not in SM at this stage

craniofacial
• at E9.5 cell proliferation in pharyngeal endoderm is reduced with cell mitotic indices decreased by 60% relative to controls
• excessive neural crest cell death is observed in pharyngeal arch mesenchyme at E9.5

cellular
• indices are reduced by 50% and 60% in splanchnic mesoderm and pharyngeal endoderm at E9.5

nervous system
• excessive neural crest cell death is observed in pharyngeal arch mesenchyme at E9.5, as well as in presumptive cardiac neural crest cells in close proximity to outflow tract

growth/size/body
• excessive neural crest cell death is observed in pharyngeal arch mesenchyme at E9.5


Mouse Genome Informatics
cn5
    Fgf8tm1.3Mrt/Fgf8tm1.4Mrt
Tg(Msx2-cre)5Rem/0

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
limbs/digits/tail
• forelimbs missing digit II or III
• hindlimb missing digit I
• forelimb digits I and V missing phalanges
• hindlimb digits II and V missing phalanges
• mildly hypoplastic
• deltoid tuberosity missing
• zeugopod elements are mildly hypoplastic (J:66266)
• radius is always absent in mutants
• stylopod is severely reduced in hindlimbs (11/19 bilaterally, 4/19 unilaterally) but only mildly affected in forelimbs (J:66266)
• zeugopod elements are mildly hypoplastic (J:66266)
• limb buds are reduced in size detected at ~E10.25
• digit I is missing in hindlimbs (13/19 bilaterally, 5/19 unilaterally) and digit II or III is missing in the forelimbs (12/19 bilaterally, 5/19 unilaterally)

skeleton
• radius is always absent in mutants

embryogenesis
• limb buds are reduced in size detected at ~E10.25

Mouse Models of Human Disease
OMIM IDRef(s)
Tetralogy of Fallot; TOF 187500 J:66266


Mouse Genome Informatics
cn6
    Fgf8tm1.3Mrt/Fgf8tm1.4Mrt
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• apoptosis in the telencephalon is increased in a qualitatively similar manner to the Fgf8 conditional KOs, but is more severe

cellular
• apoptosis in the telencephalon is increased in a qualitatively similar manner to the Fgf8 conditional KOs, but is more severe


Mouse Genome Informatics
cn7
    Fgf8tm1.2Mrt/Fgf8tm1.3Mrt
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutant mice die at birth due to defects in forebrain development

nervous system
• at birth, mutants exhibit lethal defects in forebrain development
• however, overall development of the inner ear and cochlea appeared normal

hearing/vestibular/ear
• at E18.5, IHCs and OHCs appear to be in direct contact with each other in some cochlear sections
• at E18.5, mutant mice show a significant reduction in the size and number of pillar cells (PCs) relative to control mice
• at E18.5, the distance between the lateral edge of the IHC and the medial edge of the first row OHC (a measure of the degree of PC development) is significantly decreased along the length of the cochlea
• at E18.5, PCs with weak or no lumenal projections are noted along the entire cochlear length with no region-specific variations
• at E18.5, pillar cells are missing or underdeveloped
• at E18.5, lumenal surface of the organ of Corti shows disruption of pillar cell growth and close approximation of IHCs to OHCs
• however, the overall structure of the epithelium and putative developing pillar cells are normal up to E15

cellular
• at E18.5, the distance between the lateral edge of the IHC and the medial edge of the first row OHC (a measure of the degree of PC development) is significantly decreased along the length of the cochlea
• at E18.5, PCs with weak or no lumenal projections are noted along the entire cochlear length with no region-specific variations


Mouse Genome Informatics
cn8
    Fgf8tm1.3Mrt/Fgf8tm1.4Mrt
Tg(CAG-Bgeo,-Fgf4)1Mrt/?
Tg(Msx2-cre)5Rem/?

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
limbs/digits/tail
N
• reversal of abnormalities resulting from loss of Fgf8 alone (J:104411)
• deltoid tuberosity is normal (J:104411)
• phenotype due to conditional over expression of Fgf4 retained

growth/size/body

vision/eye

reproductive system

embryogenesis

skeleton


Mouse Genome Informatics
cn9
    Fgf8tm1.3Mrt/Fgf8tm1.4Mrt
Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sortm1Sor
Nkx2-5tm1(cre)Rjs/Nkx2-5+

involves: 129P2/OlaHsd * 129S4/SvJaeSor * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• anterior heart field (AHF) cells are lost compared to controls; numbers of B-gal +ve cells in splanchnic mesoderm (SM) and pharyngeal endoderm are significantly reduced, causing thinning of these cell layers
• number of positive cells in pharyngeal arch core mesoderm (CM) is significantly decreased also

embryogenesis
• thinning of splanchnic mesoderm due to significantly reduced numbers of B-gal +ve cells


Mouse Genome Informatics
cn10
    En1tm7(cre/ESR1)Alj/0
Fgf8tm1.1Jyhl/Fgf8tm1.3Mrt

involves: 129P2/OlaHsd * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

nervous system
• a significant increase in the number of dead cells in the mesencephalon and to a less extent in rhombomere of the neural tube of embryos at the 13-somite stage
• a significant increase in the number of dead cells in rhombomere of the neural tube of embryos at the 13-somite stage
• a reduction of serotonergic neurons in raphe nuclei
• E18.5 revealed a nearly complete loss of the midbrain and the cerebellum
• a significant increase in the number of dead cells in the mesencephalon at the 13-somite stage
• depletion of dopaminergic neurons at E18.5
• E18.5 revealed a nearly complete loss of the midbrain and the cerebellum
• at E18.5 in the substantia nigra and ventral tegmental area
• at E18.5 a reduction of serotonergic neurons in the raphe nucleus

embryogenesis
• a significant increase in the number of dead cells in the mesencephalon and to a less extent in rhombomere of the neural tube of embryos at the 13-somite stage
• a significant increase in the number of dead cells in rhombomere of the neural tube of embryos at the 13-somite stage


Mouse Genome Informatics
cn11
    En1tm7(cre/ESR1)Alj/0
Fgf8tm1.3Mrt/Fgf8tm1.4Mrt

involves: 129P2/OlaHsd * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• a reduction of serotonergic neurons in raphe nuclei
• E18.5 revealed a nearly complete loss of the midbrain and the cerebellum
• depletion of dopaminergic neurons at E18.5
• E18.5 revealed a nearly complete loss of the midbrain and the cerebellum
• at E18.5 in the substantia nigra and ventral tegmental area
• at E18.5 a reduction of serotonergic neurons in the raphe nucleus


Mouse Genome Informatics
cn12
    En1tm7(cre/ESR1)Alj/0
Fgf8tm1.3Mrt/Fgf8tm2.1Jyhl
Gt(ROSA)26Sortm1Sor/0

involves: 129P2/OlaHsd * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body
N
• unlike mice homozygous for Fgf8tm2.1Jyhl, mice are normal in size (J:156717)

nervous system
N
• unlike mice homozygous for Fgf8tm2.1Jyhl, the size of the midbrain and cerebellum are normal (J:156717)


Mouse Genome Informatics
cn13
    Fgf8tm1.3Mrt/Fgf8tm1.4Mrt
Tbx1tm4(cre/Esr1*)Bld/Tbx1+

involves: 129P2/OlaHsd * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• defects are seen in 81, 88, and 89% of fetuses at E18.5 when tamoxifen is administered at E7.5, 8.5 or 9.5 respectively


Mouse Genome Informatics
cn14
    Fgf8tm1.3Mrt/Fgf8+
Tbx1tm4(cre/Esr1*)Bld/Tbx1+

involves: 129P2/OlaHsd * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• defects are seen in 52, 32, and 63% of fetuses at E18.5 when tamoxifen is administered at E7.5, 8.5 or 9.5 respectively


Mouse Genome Informatics
cn15
    Fgf8tm1.3Mrt/Fgf8tm1.4Mrt
Nkx2-5tm1(cre)Rjs/Nkx2-5+

involves: 129P2/OlaHsd * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutant embryos are present at expected ratio up to E9.5, but a marked reduction is observed at later times with no surviving mutants by E10.5

embryogenesis
• arches are hypoplastic at E9.5

cardiovascular system
• at E9.5, heart tube is severely truncated
• presumptive outflow tract (OT) is almost completely absent at E9.5; only a small segment of myocardium joins left ventricle to aortic sac
• both atria are slightly dilated at E9.5
• slightly at E9.5
• almost completely absent at E9.5

craniofacial
• arches are hypoplastic at E9.5


Mouse Genome Informatics
cn16
    Fgf8tm1.3Mrt/Fgf8tm1.4Mrt
Tg(Tnnt2-cre)5Blh/0

involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
N
• no outflow tract or right ventricle defects are observed at E10.5 and no outflow tract septation defects are seen in term fetuses (J:109474)


Mouse Genome Informatics
cn17
    Fgf8tm1.3Mrt/Fgf8tm1.4Mrt
Tg(T-cre)1Lwd/0

involves: 129P2/OlaHsd * C3H * C57BL/6 * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants die shortly after birth

renal/urinary system
• apoptosis is increased at E14.5 most prominently in the cortical mesenchyme and at E16.5 in the primitive epithelia
• no glomeruli are present at any stage of kidney development
• at E14.5 mutant kidneys show only condensation and renal vesicle formation and not tubulogenesis or glomerulogenesis that are seen in wild-type mice
• at E16.5 evidence of cap formation is mostly missing and few vesicles remain in the mutant kidneys and those remaining vesicles do not show signs of tubulogenesis
• at E18.5 the hypocellular kidney is largely devoid of nephron epithelia
• apoptosis is increased at E14.5 most prominently in the cortical mesenchyme and at E16.5 in the primitive epithelia
• at E18.5 the few remaining ureteric bud radii fail to bifurcate in the cortical nephrogenic region; however, somite formation, tendon progenitor populations fro E10.5 - E14.5, and limb bud induction are normal
• at E14.5 ureteric bud branching is dramatically reduced

limbs/digits/tail
• most mutants lack at least one hindlimb digit; however, limb bud induction is normal

skeleton
N
• no defects are seen in skeletal development including rib formation (J:101175)

cellular
• apoptosis is increased at E14.5 most prominently in the cortical mesenchyme and at E16.5 in the primitive epithelia


Mouse Genome Informatics
cn18
    Fgf8tm1.2Mrt/Fgf8tm1.3Mrt
Tg(Nes-cre)1Atp/0

involves: 129P2/OlaHsd * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants die shortly after birth; lungs do not inflate so death is probably from anoxia

embryogenesis
• at E9.0 the first branchial arch is smaller than in wild-type

cellular
• at E8.75-10 extensive cell death is observed; at E9.5 the region with dying cells stretches proximally to the trigeminal swelling and included the maxillary arch-forming region

craniofacial
• mutants have severe craniofacial defects; some mutants show a less severe phenotype with a small increase in dermal bone development and abnormalities are often observed on only one side of the head
• there is little expansion of the mandible primordia as embryos mature; growth is not completely arrested as the mandibular primordial extend distally and meet at the midline
• there is little expansion of the maxilla primordia as embryos mature
• incus and ala temporalis fail to form
• there is an ectodermal covering over the prospective mouth
• body of Meckel's cartilage fails to develop
• at E9.0 the first branchial arch is smaller than in wild-type
• newborns have small disorganized tongues
• molars are absent but vestigal lower incisors are present in association with the rostral process

nervous system
• the mandibular division of the trigeminal nerve is truncated and misrouted

hearing/vestibular/ear
• incus and ala temporalis fail to form

digestive/alimentary system
• newborns have small disorganized tongues

skeleton
• there is little expansion of the mandible primordia as embryos mature; growth is not completely arrested as the mandibular primordial extend distally and meet at the midline
• there is little expansion of the maxilla primordia as embryos mature
• incus and ala temporalis fail to form
• body of Meckel's cartilage fails to develop

growth/size/body
• newborns have small disorganized tongues
• molars are absent but vestigal lower incisors are present in association with the rostral process


Mouse Genome Informatics
cn19
    Fgf8tm1.3Mrt/Fgf8tm1.4Mrt
Tg(Tbx1-cre)1Joe/0

Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• most mice die between E18.5 and P1

cardiovascular system
N
• some defects observed as a result of Tbx1-deficiency, including those involving the aortic arch, were not observed (J:88814)
• exhibit variable cardiovascular patterning defects listed below
• duplication of the internal carotid arteries
• impaired differentiation in the great vessels
• muscular wall is of variable thickness and lacks the striated structural appearance of normal arterial smooth muscle
• Tetrology of Fallot
• atrial septal defects
• ventricular septal defects

immune system
• some exhibit a single lobed thymus

muscle
• impaired differentiation in the great vessels
• muscular wall is of variable thickness and lacks the striated structural appearance of normal arterial smooth muscle

hematopoietic system
• some exhibit a single lobed thymus

endocrine/exocrine glands
• some exhibit a single lobed thymus

Mouse Models of Human Disease
OMIM IDRef(s)
DiGeorge Syndrome; DGS 188400 J:88814