Phenotypes associated with this allele

• Allele Symbol: Tg(EIIa-cre)C5379Lmgd
• Allele Name: transgene insertion C5379, Laboratory of Mammalian Genes and Development, Heiner Westphal
• Allele ID: MGI:2137691
• Summary: 55 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Cdkn1c^tm2.1Kei/Cdkn1c^+ Tg(EIIa-cre)C5379Lmgd/0	B6.Cg-Cdkn1c^tm2.1Kei Tg(EIIa-cre)C5379Lmgd	MGI:5294432
cn2	Fgfr2^tm1Ewj/Fgfr2^+ Tg(EIIa-cre)C5379Lmgd/0	B6.Cg-Fgfr2^tm1Ewj Tg(EIIa-cre)C5379Lmgd	MGI:4440857
cn3	Fgfr2^tm2Ewj/Fgfr2^+ Tg(EIIa-cre)C5379Lmgd/0	B6.Cg-Fgfr2^tm2Ewj Tg(EIIa-cre)C5379Lmgd	MGI:4440856
cn4	Mfn2^tm1Dcc/Mfn2^tm3Dcc Tg(EIIa-cre)C5379Lmgd/0	involves: 129 * 129S4/SvJaeSor * Black Swiss * FVB/N	MGI:3779092
cn5	Mfn1^tm1Dcc/Mfn1^tm2Dcc Tg(EIIa-cre)C5379Lmgd/0	involves: 129 * 129S4/SvJaeSor * Black Swiss * FVB/N	MGI:3779085
cn6	Robo2^tm1Rilm/Robo2^tm1.1Rilm Tg(EIIa-cre)C5379Lmgd/?	involves: 129 * C57BL/6 * FVB/N	MGI:3759462
cn7	Cfp^tm2.1Song/Cfp^tm2.1Song Tg(EIIa-cre)C5379Lmgd/0	involves: 129 * C57BL/6 * FVB/N * SJL	MGI:4838305
cn8	Fgf13^tm1Xuzh/Y Tg(EIIa-cre)C5379Lmgd/0	involves: 129 * FVB/N	MGI:5433298
cn9	Fgf13^tm1Xuzh/Fgf13^tm1Xuzh Tg(EIIa-cre)C5379Lmgd/0	involves: 129 * FVB/N	MGI:5433299
cn10	Cacna1a^tm2.1Maag/Cacna1a^tm2.2Maag Tg(EIIa-cre)C5379Lmgd/0	involves: 129P2/OlaHsd * FVB/N	MGI:3697450
cn11	Slc6a9^tm1Veul/Slc6a9^tm1Veul Tg(EIIa-cre)C5379Lmgd/?	involves: 129P2/OlaHsd * FVB/N	MGI:4818487
cn12	Gata6^tm2.1Sad/Gata6^tm2.2Sad Tg(EIIa-cre)C5379Lmgd/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * FVB/N * SJL	MGI:3662656
cn13	Gba1^tm1Clk/Gba1^tm1.1Clk Tg(EIIa-cre)C5379Lmgd/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N	MGI:3699180
cn14	Fgfr2^tm1Ewj/Fgfr2^+ Tg(EIIa-cre)C5379Lmgd/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N	MGI:3604025
cn15	Pelo^tm2Imad/Pelo^tm2Imad Tg(EIIa-cre)C5379Lmgd/?	involves: 129S1/Sv * 129X1/SvJ * FVB/N	MGI:5705483
cn16	Piga^tm1Bsl/Piga^+ Tg(EIIa-cre)C5379Lmgd/0	involves: 129S1/Sv * FVB/NJ	MGI:3814198
cn17	Tg(EIIa-cre)C5379Lmgd/0 Tg(Rnu6-RNAi:Bccip)4Zshn/0 Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas * C57BL/6 * FVB/N	MGI:5292118
cn18	Drd1^tm2Jcd/Drd1^+ Tg(EIIa-cre)C5379Lmgd/0	involves: 129S4/SvJae * BALB/c * CD-1 * FVB/N	MGI:3709752
cn19	Porcn^tm1.1Vdv/Y Tg(EIIa-cre)C5379Lmgd/0	involves: 129S4/SvJaeSor * 129S5/SvEvBrd * C57BL/6J * FVB/N	MGI:5435562
cn20	Porcn^tm1.1Vdv/Porcn^+ Tg(EIIa-cre)C5379Lmgd/0	involves: 129S4/SvJaeSor * 129S5/SvEvBrd * C57BL/6J * FVB/N	MGI:5435561
cn21	Ccn2^tm2Mae/Ccn2^+ Tg(EIIa-cre)C5379Lmgd/?	involves: 129S6/SvEvTac	MGI:4838160
cn22	Tgfb3^tm1Moaz/Tgfb3^tm1.1Moaz Tg(EIIa-cre)C5379Lmgd/0	involves: 129S6/SvEvTac * Black Swiss * C57BL/6J * FVB/N	MGI:5313418
cn23	Cbfb^tm1Lhc/Cbfb^+ Tg(EIIa-cre)C5379Lmgd/0	involves: 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:3615451
cn24	Ccn2^tm2Mae/Ccn2^+ Tg(EIIa-cre)C5379Lmgd/?	involves: 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:4838158
cn25	Sox11^tm1.1Gan/Sox11^tm1.1Gan Tg(EIIa-cre)C5379Lmgd/0	involves: 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:5827939
cn26	Zfhx3^tm1.1Jtd/Zfhx3^+ Tg(EIIa-cre)C5379Lmgd/0	involves: 129S6/SvEvTac * C57BL/6 * FVB/N * SJL	MGI:5446521
cn27	Fgfr2^tm2Cxd/Fgfr2^+ Tg(EIIa-cre)C5379Lmgd/0	involves: 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:5790180
cn28	Del(XMagea1-Magea6)1Nju/Y Tg(EIIa-cre)C5379Lmgd/0	involves: 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:5902066
cn29	Egfr^tm1Dwt/Egfr^tm1Dwt Tg(EIIa-cre)C5379Lmgd/0	involves: 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:3834095
cn30	Erbb3^tm1Squ/Erbb3^tm1Squ Tg(EIIa-cre)C5379Lmgd/0	involves: 129S6/SvEvTac * FVB/N	MGI:3691285
cn31	Fgfr2^tm2Cxd/Fgfr2^+ Tg(EIIa-cre)C5379Lmgd/0	involves: 129S6/SvEvTac * FVB/N	MGI:3604078
cn32	Ptpn11^tm6Bgn/Ptpn11^+ Tg(EIIa-cre)C5379Lmgd/0	involves: 129S6/SvEvTac * FVB/N	MGI:3845015
cn33	Arhgap6/Hccs/Mid1^tm1Hzo/Arhgap6/Hccs/Mid1^tm1Hzo Tg(EIIa-cre)C5379Lmgd/?	involves: 129S7/SvEvBrd * C57BL/6 * FVB/N	MGI:3580087
cn34	Arhgap6/Hccs/Mid1^tm1Hzo/Y Tg(EIIa-cre)C5379Lmgd/?	involves: 129S7/SvEvBrd * C57BL/6 * FVB/N	MGI:3580088
cn35	Arhgap6/Hccs/Mid1^tm1Hzo/Arhgap6/Hccs/Mid1^tm1Hzo Tg(EIIa-cre)C5379Lmgd/?	involves: 129S7/SvEvBrd * C57BL/6 * FVB/N	MGI:3580085
cn36	Arhgap6/Hccs/Mid1^tm1Hzo/Arhgap6/Hccs/Mid1^tm1Hzo Tg(EIIa-cre)C5379Lmgd/?	involves: 129S7/SvEvBrd * C57BL/6 * FVB/N	MGI:3580089
cn37	Arhgap6/Hccs/Mid1^tm1Hzo/Y Tg(EIIa-cre)C5379Lmgd/?	involves: 129S7/SvEvBrd * C57BL/6 * FVB/N	MGI:3580090
cn38	Arhgap6/Hccs/Mid1^tm1Hzo/Mid1^+ Tg(EIIa-cre)C5379Lmgd/?	involves: 129S7/SvEvBrd * C57BL/6 * FVB/N	MGI:3580091
cn39	Arhgap6/Hccs/Mid1^tm1Hzo/Hccs^+ Tg(EIIa-cre)C5379Lmgd/?	involves: 129S7/SvEvBrd * C57BL/6 * FVB/N	MGI:3580092
cn40	Arhgap6/Hccs/Mid1^tm1Hzo/Arhgap6^+ Tg(EIIa-cre)C5379Lmgd/?	involves: 129S7/SvEvBrd * C57BL/6 * FVB/N	MGI:3580093
cn41	Arhgap6/Hccs/Mid1^tm1Hzo/Y Tg(EIIa-cre)C5379Lmgd/?	involves: 129S7/SvEvBrd * C57BL/6 * FVB/N	MGI:3580086
cn42	Inhba^tm1Zuk/Inhba^tm3Zuk Tg(EIIa-cre)C5379Lmgd/?	involves: 129S7/SvEvBrd * C57BL/6J * FVB/N	MGI:3758885
cn43	Tet2^tm1.1Iaai/Tet2^tm1.1Iaai Tg(EIIa-cre)C5379Lmgd/0	involves: 129S/SvEv * C57BL/6 * FVB/N	MGI:5141143
cn44	Wls^tm1.1Lan/Wls^tm1.1Lan Tg(EIIa-cre)C5379Lmgd/0	involves: 129S/SvEv * FVB/N * SJL	MGI:4838404
cn45	Igf1^tm1Dlr/Igf1^tm1Dlr Tg(EIIa-cre)C5379Lmgd/0	involves: 129/Sv * C57BL/6 * FVB/N	MGI:2176942
cn46	Rnu11^tm1.1Rank/Rnu11^tm1.1Rank Tg(EIIa-cre)C5379Lmgd/0	involves: 129X1/SvJ * FVB/N	MGI:6393909
cn47	Serpina1a^tm1Amgh/Serpina1a^tm1Amgh Tg(EIIa-cre)C5379Lmgd/0	involves: 129X1/SvJ * FVB/N	MGI:5566808
cn48	Fbxw7^tm2Iaai/Fbxw7^+ Tg(EIIa-cre)C5379Lmgd/0	involves: C57BL/6 * FVB/N	MGI:5524228
cn49	Tg(EIIa-cre)C5379Lmgd/0 Tg(Rnu6-RNAi:Bccip)4Zshn/0	involves: C57BL/6 * FVB/N	MGI:5292117
cn50	Epo^tm1Knni/Epo^tm1Knni Tg(EIIa-cre)C5379Lmgd/0	involves: C57BL/6 * FVB/N	MGI:4839527
cn51	Gna13^tm2.2Soff/Gna13^tm2.2Soff Tg(EIIa-cre)C5379Lmgd/?	involves: FVB	MGI:3712472
cn52	Pawr^tm1Yshi/Pawr^tm1Yshi Tg(EIIa-cre)C5379Lmgd/?	involves: FVB/N	MGI:3714177
cn53	Becn1^tm1Ebr/Becn1^+ Tg(EIIa-cre)C5379Lmgd/?	involves: FVB/N	MGI:5308738
cx54	Tg(EIIa-cre)C5379Lmgd/? Trip11^tm1.2Psmi/Trip11^tm1.2Psmi	involves: 129/Sv * C57BL/6 * FVB/N	MGI:6154152
cx55	Scnm1^tm1.1Mm/Scnm1^tm1.1Mm Tg(EIIa-cre)C5379Lmgd/0	involves: C57BL/6 * C57BL/6J * FVB * SJL	MGI:3818063

Genotype
MGI:5294432

cn1

• Allelic Composition: Cdkn1c^tm2.1Kei/Cdkn1c⁺; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: B6.Cg-Cdkn1c^tm2.1Kei Tg(EIIa-cre)C5379Lmgd

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

renal/urinary system

kidney papillary atrophy ( J:176209 )

• when Cdkn1c^tm2.1Kei is inherited maternally, mice exhibit atrophy of the renal papilla compared with control mice

Genotype
MGI:4440857

cn2

• Allelic Composition: Fgfr2^tm1Ewj/Fgfr2⁺; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: B6.Cg-Fgfr2^tm1Ewj Tg(EIIa-cre)C5379Lmgd

Skull analysis of Fgfr2^tm2Ewj/Fgfr2⁺ Tg(EIIa-cre)C5379Lmgd/0 and Fgfr2^tm1Ewj/Fgfr2⁺ Tg(EIIa-cre)C5379Lmgd/0 mice

skeleton

enhanced osteoblast differentiation ( J:158773 )

• as determined by marker expression, osteoblast differentiation at the chondro-osseuous junction and the metaphysis is increased compared to in wild-type mice

increased osteoblast proliferation ( J:158773 )

• osteoblast proliferation at the chondro-osseuous junction and the metaphysis is increased compared to in wild-type mice

abnormal cranial suture morphology ( J:158773 )

• the suture between the horizontal plate of the palatine bone and palatal process of the maxilla is fused unlike in wild-type mice

abnormal coronal suture morphology ( J:158773 )

• coronal sutures exhibit increased osteogenic differentiation and accelerated bone growth compared to in wild-type mice

• however, apoptosis rates at coronal sutures is normal

abnormal intermaxillary suture morphology ( J:158773 )

• the inter-premaxillary suture appears patent unlike in wild-type mice

abnormal maxillary-premaxillary suture morphology ( J:158773 )

• mice exhibit premature closure of the premaxillary-maxillary sutures unlike wild-type mice

increased cranium height ( J:158773 )

• skull height is increased compared to in wild-type mice

small cranium ( J:158773 )

short mandible ( J:158773 )

short maxilla ( J:158773 )

• mice exhibit shorter maxilla than wild-type and cre-recombined Fgfr2^tm2Ewj heterozygotes

short nasal bone ( J:158773 )

• the nasal region is shorter than in wild-type mice

premature coronal suture closure ( J:158773 )

• at P0, mice exhibit coronal suture presynostosis or synostosis unlike wild-type mice

premature zygomaticomaxillary suture closure ( J:158773 )

• mice exhibit premature closure of the suture between the zygomatic process of the maxilla and the zygomatic bones unlike wild-type mice

craniofacial

abnormal cranial suture morphology ( J:158773 )

• the suture between the horizontal plate of the palatine bone and palatal process of the maxilla is fused unlike in wild-type mice

abnormal coronal suture morphology ( J:158773 )

• coronal sutures exhibit increased osteogenic differentiation and accelerated bone growth compared to in wild-type mice

• however, apoptosis rates at coronal sutures is normal

abnormal intermaxillary suture morphology ( J:158773 )

• the inter-premaxillary suture appears patent unlike in wild-type mice

abnormal maxillary-premaxillary suture morphology ( J:158773 )

• mice exhibit premature closure of the premaxillary-maxillary sutures unlike wild-type mice

increased cranium height ( J:158773 )

• skull height is increased compared to in wild-type mice

small cranium ( J:158773 )

short mandible ( J:158773 )

short maxilla ( J:158773 )

• mice exhibit shorter maxilla than wild-type and cre-recombined Fgfr2^tm2Ewj heterozygotes

short nasal bone ( J:158773 )

• the nasal region is shorter than in wild-type mice

abnormal palate morphology ( J:158773 )

• the most posterior portion of the palate is reduced compared to in wild-type mice

abnormal palatal shelf fusion at midline ( J:158773 )

• the midline suture between the horizontal plates of the palatine bones is patent compared to controls

• in 1 of 8 mice the suture between the horizontal plate of the palatine bone and the palatal shelf of the maxilla is patent compared with 7 of 12 wild-type mice

decreased palatal length ( J:158773 )

• mice exhibit shorter palate than wild-type and cre-recombined Fgfr2^tm2Ewj heterozygotes

digestive/alimentary system

abnormal palate morphology ( J:158773 )

• the most posterior portion of the palate is reduced compared to in wild-type mice

abnormal palatal shelf fusion at midline ( J:158773 )

• the midline suture between the horizontal plates of the palatine bones is patent compared to controls

• in 1 of 8 mice the suture between the horizontal plate of the palatine bone and the palatal shelf of the maxilla is patent compared with 7 of 12 wild-type mice

decreased palatal length ( J:158773 )

• mice exhibit shorter palate than wild-type and cre-recombined Fgfr2^tm2Ewj heterozygotes

cellular

enhanced osteoblast differentiation ( J:158773 )

• as determined by marker expression, osteoblast differentiation at the chondro-osseuous junction and the metaphysis is increased compared to in wild-type mice

increased osteoblast proliferation ( J:158773 )

• osteoblast proliferation at the chondro-osseuous junction and the metaphysis is increased compared to in wild-type mice

vision/eye

decreased inner canthal distance ( J:158773 )

• intercanthal distance is reduced compared to in wild-type mice

growth/size/body

short nasal bone ( J:158773 )

• the nasal region is shorter than in wild-type mice

abnormal palate morphology ( J:158773 )

• the most posterior portion of the palate is reduced compared to in wild-type mice

abnormal palatal shelf fusion at midline ( J:158773 )

• the midline suture between the horizontal plates of the palatine bones is patent compared to controls

• in 1 of 8 mice the suture between the horizontal plate of the palatine bone and the palatal shelf of the maxilla is patent compared with 7 of 12 wild-type mice

decreased palatal length ( J:158773 )

• mice exhibit shorter palate than wild-type and cre-recombined Fgfr2^tm2Ewj heterozygotes

respiratory system

short nasal bone ( J:158773 )

• the nasal region is shorter than in wild-type mice

Genotype
MGI:4440856

cn3

• Allelic Composition: Fgfr2^tm2Ewj/Fgfr2⁺; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: B6.Cg-Fgfr2^tm2Ewj Tg(EIIa-cre)C5379Lmgd

Skeletal abnormalities in Fgfr2^tm2Ewj/Fgfr2⁺ Tg(EIIa-cre)C5379Lmgd/0 mice

mortality/aging

postnatal lethality, complete penetrance ( J:158773 )

• almost half of all mice die within 24 to 36 hours of birth

• most mice die within 2 weeks of birth with very few surviving to 3 weeks

skeleton

abnormal cranial suture morphology ( J:158773 )

• mice exhibit a patent inter-premaxillary suture with fusion of the premaxilla-maxillary sutures unlike wild-type mice

• mice exhibit premature closure of the suture between the zygomatic process of the maxilla and the zygomatic bones and the premaxillary-maxillary sutures unlike wild-type mice

abnormal lambdoid suture morphology ( J:158773 )

• with proximate osteogenic fronts and cellular disorganization at P0

abnormal sagittal suture morphology ( J:158773 )

• at E16.5 to P0, mice exhibit ectopic cartilage at the sagittal suture unlike wild-type mice

short basicranium ( J:158773 )

• the anterior and overall length of the cranial base is decreased compared to in wild-type mice

increased cranium height ( J:158773 )

• skull height is increased compared to in wild-type mice

small cranium ( J:158773 )

short mandible ( J:158773 )

abnormal maxillary zygomatic process morphology ( J:158773 )

• the zygomatic process of the maxilla and malar bone are fused unlike in wild-type mice

short maxilla ( J:158773 )

short nasal bone ( J:158773 )

• the nasal region is shorter than in wild-type mice and cre-recombined Fgfr2^tm1Ewj heterozygotes

abnormal zygomatic bone morphology ( J:158773 )

• the zygomatic process of the maxilla and malar bone are fused unlike in wild-type mice

domed cranium ( J:158773 )

short humerus ( J:158773 )

• at P10

short radius ( J:158773 )

• at P10

short femur ( J:158773 )

• at P10

short tibia ( J:158773 )

• at P10

abnormal sternum morphology ( J:158773 )

• at P0, all mice exhibit bony fusions of the sternum unlike wild-type mice

abnormal skeleton development ( J:158773 )

• coronal sutures exhibit increased osteogenic differentiation and accelerated bone growth compared to in wild-type mice

• however, apoptosis rates at coronal sutures is normal

• at E17.5 to P0, the physis hypertrophic zone is disorganized compared to in wild-type mice

enhanced osteoblast differentiation ( J:158773 )

• as determined by marker expression at E19, osteoblast differentiation at the chondro-osseuous junction and the metaphysis is increased compared to in wild-type mice

synostosis ( J:158773 )

abnormal skeleton physiology ( J:158773 )

increased osteoblast proliferation ( J:158773 )

• at E19, osteoblast proliferation at the chondro-osseuous junction and the metaphysis is increased compared to in wild-type mice

premature coronal suture closure ( J:158773 )

• mice exhibit unilateral or bilateral coronal synostosis unlike wild-type mice

• at P0, mice exhibit coronal suture presynostosis unlike wild-type mice

craniofacial

abnormal cranial suture morphology ( J:158773 )

• mice exhibit a patent inter-premaxillary suture with fusion of the premaxilla-maxillary sutures unlike wild-type mice

• mice exhibit premature closure of the suture between the zygomatic process of the maxilla and the zygomatic bones and the premaxillary-maxillary sutures unlike wild-type mice

abnormal lambdoid suture morphology ( J:158773 )

• with proximate osteogenic fronts and cellular disorganization at P0

abnormal sagittal suture morphology ( J:158773 )

• at E16.5 to P0, mice exhibit ectopic cartilage at the sagittal suture unlike wild-type mice

short basicranium ( J:158773 )

• the anterior and overall length of the cranial base is decreased compared to in wild-type mice

increased cranium height ( J:158773 )

• skull height is increased compared to in wild-type mice

small cranium ( J:158773 )

short mandible ( J:158773 )

abnormal maxillary zygomatic process morphology ( J:158773 )

• the zygomatic process of the maxilla and malar bone are fused unlike in wild-type mice

short maxilla ( J:158773 )

short nasal bone ( J:158773 )

• the nasal region is shorter than in wild-type mice and cre-recombined Fgfr2^tm1Ewj heterozygotes

abnormal zygomatic bone morphology ( J:158773 )

• the zygomatic process of the maxilla and malar bone are fused unlike in wild-type mice

domed cranium ( J:158773 )

abnormal palatal shelf fusion at midline ( J:158773 )

• from E15.5 to P0, all mice exhibit bilaterally incomplete fusion at the junction of the primary and secondary palatal shelves unlike in wild-type mice

• the midline suture between the horizontal plates of the palatine bones is patent unlike in wild-type mice

• in 9 of 10 mice the suture between the horizontal plate of the palatine bone and the palatal shelf of the maxilla is patent compared with 3 of 7 wild-type mice

decreased palatal length ( J:158773 )

growth/size/body

short nasal bone ( J:158773 )

• the nasal region is shorter than in wild-type mice and cre-recombined Fgfr2^tm1Ewj heterozygotes

abnormal palatal shelf fusion at midline ( J:158773 )

• from E15.5 to P0, all mice exhibit bilaterally incomplete fusion at the junction of the primary and secondary palatal shelves unlike in wild-type mice

• the midline suture between the horizontal plates of the palatine bones is patent unlike in wild-type mice

• in 9 of 10 mice the suture between the horizontal plate of the palatine bone and the palatal shelf of the maxilla is patent compared with 3 of 7 wild-type mice

decreased palatal length ( J:158773 )

decreased body weight ( J:158773 )

• beginning at P5

postnatal growth retardation ( J:158773 )

digestive/alimentary system

abnormal palatal shelf fusion at midline ( J:158773 )

• from E15.5 to P0, all mice exhibit bilaterally incomplete fusion at the junction of the primary and secondary palatal shelves unlike in wild-type mice

• the midline suture between the horizontal plates of the palatine bones is patent unlike in wild-type mice

• in 9 of 10 mice the suture between the horizontal plate of the palatine bone and the palatal shelf of the maxilla is patent compared with 3 of 7 wild-type mice

decreased palatal length ( J:158773 )

limbs/digits/tail

short humerus ( J:158773 )

• at P10

short radius ( J:158773 )

• at P10

short femur ( J:158773 )

• at P10

short tibia ( J:158773 )

• at P10

cellular

enhanced osteoblast differentiation ( J:158773 )

• as determined by marker expression at E19, osteoblast differentiation at the chondro-osseuous junction and the metaphysis is increased compared to in wild-type mice

increased osteoblast proliferation ( J:158773 )

• at E19, osteoblast proliferation at the chondro-osseuous junction and the metaphysis is increased compared to in wild-type mice

vision/eye

decreased inner canthal distance ( J:158773 )

• intercanthal distance is reduced compared to in wild-type mice

respiratory system

short nasal bone ( J:158773 )

• the nasal region is shorter than in wild-type mice and cre-recombined Fgfr2^tm1Ewj heterozygotes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acrocephalosyndactylia		DOID:12960	OMIM:101200	J:158773

Genotype
MGI:3779092

cn4

• Allelic Composition: Mfn2^tm1Dcc/Mfn2^tm3Dcc; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129 * 129S4/SvJaeSor * Black Swiss * FVB/N

mortality/aging

prenatal lethality, complete penetrance ( J:132329 )

• embryos die during mid-gestation similar to Mfn2^tm1Dcc homozygous embryos

Genotype
MGI:3779085

cn5

• Allelic Composition: Mfn1^tm1Dcc/Mfn1^tm2Dcc; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129 * 129S4/SvJaeSor * Black Swiss * FVB/N

mortality/aging

prenatal lethality, complete penetrance ( J:132329 )

• embryos die during mid-gestation similar to Mfn1^tm1Dcc homozygous embryos

Genotype
MGI:3759462

cn6

• Allelic Composition: Robo2^tm1Rilm/Robo2^tm1.1Rilm; Tg(EIIa-cre)C5379Lmgd/?
• Genetic Background: involves: 129 * C57BL/6 * FVB/N

renal/urinary system

abnormal renal/urinary system morphology ( J:125214 )

• mice exhibit unilateral urinary tract abnormalities, including short ureter, megaureter, and hydronephrosis

kidney cyst ( J:125214 )

• kidney parenchyma is replaced by large cysts

hydronephrosis ( J:125214 )

• ureterovesical junctions associated with obstructions lead to megaureter and hydronephrosis

abnormal ureter morphology ( J:125214 )

• in some males the ureter is connected to the vas deferens resulting in massive hydronephrosis

large ureter ( J:125214 )

• ureterovesical junctions associated with obstructions lead to megaureter and hydronephrosis

short ureter ( J:125214 )

abnormal ureterovesical junction morphology ( J:125214 )

• 7 of 10 mice exhibit bilateral ureterovesical junction defects, where one UVJ is typically located laterally and cephalad in the bladder (commonly associated with reflux in man) whereas the contralateral UVJ is located caudad in the bladder or even ectopically in the urethra

ureterovesical junction obstruction ( J:125214 )

• the caudal UVJ location is associated with obstruction, leading to megaureter and severe hydronephrosis

reproductive system

abnormal vas deferens morphology ( J:125214 )

♂ • in some males the ureter is connected to the vas deferens resulting in massive hydronephrosis

growth/size/body

kidney cyst ( J:125214 )

• kidney parenchyma is replaced by large cysts

Genotype
MGI:4838305

cn7

• Allelic Composition: Cfp^tm2.1Song/Cfp^tm2.1Song; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/N * SJL

immune system

impaired complement alternative pathway ( J:165497 )

♀ • LPS-induced alternative pathway (AP) complement activation is impaired unlike in wild-type mice

Genotype
MGI:5433298

cn8

• Allelic Composition: Fgf13^tm1Xuzh/Y; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129 * FVB/N

nervous system

abnormal hippocampus morphology ( J:186253 )

♂ • mice exhibit impaired hippocampal development compared with wild-type mice

♂ • however, positioning of hippocampal neurons is normal by P30

abnormal dentate gyrus morphology ( J:186253 )

♂ • mice exhibit loosely packed neurons in the granule cell layer of the dentrate gyrus compared with wild-type mice

♂ • the dentate gyrus exhibit increased neuron numbers in the polymorphic layer compared with in wild-type mice

abnormal cerebellar granule cell morphology ( J:186253 )

♂ • mice exhibit loosely packed neurons in the granule cell layer of the dentrate gyrus compared with wild-type mice

abnormal neuron morphology ( J:186253 )

♂ • neurons exhibit impaired stabilization of microtubule organization in growth cones compared with wild-type cells

abnormal cerebral cortex pyramidal cell morphology ( J:186253 )

♂ • at E18, Cux1+ neurons are mislocalized in the deep layers of the lateral somatosensory cortex compared to in wild-type mice

♂ • mice exhibit more loosely arrayed neurons with irregular inner and outer borders in the C1 pyramidal layer compared to in wild-type mice

decreased neuron number ( J:186253 )

♂ • reduced Cux1+ cells

♂ • however, the number of Cux1+ neurons are normal at P14 and during adulthood

increased neuron number ( J:186253 )

♂ • Tbr1+ neurons in the deep layer is increased compared to in wild-type mice

behavior/neurological

abnormal spatial learning ( J:186253 )

♂ • in a Morris water maze

abnormal spatial working memory ( J:186253 )

♂ • in a Morris water maze

Genotype
MGI:5433299

cn9

• Allelic Composition: Fgf13^tm1Xuzh/Fgf13^tm1Xuzh; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129 * FVB/N

behavior/neurological

abnormal spatial learning ( J:186253 )

♀ • in a Morris water maze

abnormal spatial working memory ( J:186253 )

♀ • in a Morris water maze

nervous system

abnormal neuron morphology ( J:186253 )

♀ • neurons exhibit impaired stabilization of microtubule organization in growth cones compared with wild-type cells

Genotype
MGI:3697450

cn10

• Allelic Composition: Cacna1a^tm2.1Maag/Cacna1a^tm2.2Maag; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

lethality at weaning, complete penetrance ( J:117062 )

• die around P20-22 if left unaided

behavior/neurological

dystonia ( J:117062 )

• progressive, severe dystonia starting around P10-12

ataxia ( J:117062 )

• progressive, severe ataxia starting around P10-12

nervous system

abnormal synaptic acetylcholine release ( J:117062 )

• acetylcholine release is insensitive to 200 nM omega-Agatoxin-IVA in neuromuscular junctions

decreased neurotransmitter release ( J:117062 )

• about a 40% reduction in quantal content in neuromuscular junctions

growth/size/body

decreased body size ( J:117062 )

• at P20

muscle

dystonia ( J:117062 )

• progressive, severe dystonia starting around P10-12

Genotype
MGI:4818487

cn11

• Allelic Composition: Slc6a9^tm1Veul/Slc6a9^tm1Veul; Tg(EIIa-cre)C5379Lmgd/?
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

neonatal lethality, complete penetrance ( J:161993 )

• die within 8 hours of birth

muscle

hypotonia ( J:161993 )

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:161993 )

Genotype
MGI:3662656

cn12

• Allelic Composition: Gata6^tm2.1Sad/Gata6^tm2.2Sad; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * FVB/N * SJL

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:111388 )

• between E8.5 and E11.5 all Cre positive double mutants appear to be partially resorbed empty decidual masses

Genotype
MGI:3699180

cn13

• Allelic Composition: Gba1^tm1Clk/Gba1^tm1.1Clk; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:117763 )

• tissue glucocerebrosidase activity is reduced to ~30% of control levels except in spleen (38%) and peripheral white cells (45%)

Genotype
MGI:3604025

cn14

• Allelic Composition: Fgfr2^tm1Ewj/Fgfr2⁺; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N

mortality/aging

neonatal lethality, complete penetrance ( J:101174 )

• mutants with complete recombination die within 24 -36 hours of birth; however, 2 mutants with only partial recombination survived to adulthood

respiratory system

abnormal nasal bone morphology ( J:101174 )

• dysmorphology of the nasal bones is seen in mutants with only partial recombination at 10 months of age

pulmonary alveolar proteinosis ( J:101174 )

• presence of proteinaceous fluid in the alveoli is observed

bronchiolectasis ( J:101174 )

• multifocal and acute bronchiolectasis with mild dilation of the bronchioles are seen in mutants with complete recombination

atelectasis ( J:101174 )

• moderate and diffuse atelectasis with lack of alveolar expansion and the presence of proteinaceous fluid in the alveoli is observed

abnormal tracheal cartilage morphology ( J:101174 )

• a complete cartilage sleeve surrounds the trachea in mutants with complete recombination

respiratory failure ( J:101174 )

• seen in mutants with complete recombination

skeleton

abnormal osteoblast differentiation ( J:101174 )

• at E18.5 in mutants with complete recombination, markers of osteoblast differentiation are seen in cells from the edge of the bone plates into the mid-sutural area of the saggital suture where preosteoblasts are not normally found

• at E18.5 in mutants with complete recombination no differentiating osteoblasts are found between the osteogenic fronts unlike in wild-type mice

abnormal craniofacial bone morphology ( J:101174 )

abnormal cranial suture morphology ( J:101174 )

• in mutants with only partial recombination at 10 months of age multiple interfrontal suture defects are seen and the fronto-premaxillary, premaxillary-maxillary, and nasal-frontal sutures are obliterated

wide metopic suture ( J:101174 )

• at P1 in mutants with complete recombination the space between the osteogenic fronts is increased

• at E18.5 in mutants with complete recombination increased numbers of proliferating cells are seen between the osteogenic fronts and no differentiating osteoblasts are found between the osteogenic fronts unlike in wild-type mice

abnormal sagittal suture morphology ( J:101174 )

• at E16.5 and E18.5 in mutants with complete recombination ectopic cartilage is found along all (E16.5) or over half (E18.5) of the length of the suture

• at E18.5 in mutants with complete recombination the space between the osteogenic fronts is decreased and at P1 the osteogenic fronts are very close and osteoid is deposited between the fronts prior to synostosis

• at E18.5 and P1 in mutants with complete recombination twice as many proliferating cells are seen and some of these cells are abnormally distributed in the space between the osteogenic fronts

• at E18.5 in mutants with complete recombination, markers of osteoblast differentiation are seen in cells from the edge of the bone plates into the mid-sutural area of the saggital suture where preosteoblasts are not normally found

abnormal basicranium morphology ( J:101174 )

• increased cartilage is found on the basicranium at birth in mutants with complete recombination

• structures of the basicranium are about 30-40% smaller in mutants with only partial recombination at 10 months of age

decreased cranium height ( J:101174 )

• skull height is significantly reduced in mutants with complete recombination

decreased cranium length ( J:101174 )

• skull length is significantly reduced in mutants with complete recombination

small cranium ( J:101174 )

• skull length and height are significantly reduced in mutants with complete recombination

• in mutants with only partial recombination at 10 months of age skull width is more affected than skull length resulting in a brachycephalic skull shape

abnormal interparietal bone morphology ( J:101174 )

• the interparietal bone is compressed superiorly at the lambdoid suture in mutants with only partial recombination at 10 months of age

parietal bossing ( J:101174 )

• the parietal bones have an obvious superior bulge in mutants with only partial recombination at 10 months of age

abnormal zygomatic arch morphology ( J:101174 )

• the temporal process of the zygomatic bone is fused to the zygomatic process of the temporal bone in mutants with complete recombination

small neurocranium ( J:101174 )

• structures of the neurocranium are about 30-40% smaller in mutants with only partial recombination at 10 months of age

abnormal mandible morphology ( J:101174 )

abnormal mandibular angle morphology ( J:101174 )

• dysmorphic angular process in mutants with only partial recombination at 10 months of age

small mandible ( J:101174 )

• the mandible is very small in mutants with only partial recombination at 10 months of age

abnormal maxillary frontal process morphology ( J:101174 )

• the frontal process of the maxilla has an abnormally large sinus and bowing of the medial wall in mutants with only partial recombination at 10 months of age

abnormal maxillary zygomatic process morphology ( J:101174 )

• the zygomatic process is bowed more laterally in mutants with only partial recombination at 10 months of age

short maxilla ( J:101174 )

• seen in mutants with complete recombination

abnormal nasal bone morphology ( J:101174 )

• dysmorphology of the nasal bones is seen in mutants with only partial recombination at 10 months of age

decreased osteoclast cell number ( J:101174 )

• in mutants with complete recombination, a decrease in osteoclast numbers is seen at the chondro-osseous junction in long bones

abnormal cartilage morphology ( J:101174 )

• the nasal cartilage is thickened

abnormal tracheal cartilage morphology ( J:101174 )

• a complete cartilage sleeve surrounds the trachea in mutants with complete recombination

abnormal cartilage development ( J:101174 )

• in mutants with complete recombination, more prominent cartilage mineralization is seen in the long bones at P1; however, limb lengths are proportional to body size and no syndactyly is seen

abnormal long bone hypertrophic chondrocyte zone ( J:101174 )

• in mutants with complete recombination, the hypertrophic zone of the growth plate of the long bones is subtly irregular

premature cranial suture closure ( J:101174 )

• seen in 6 of 9 mutants with complete recombination

premature coronal suture closure ( J:101174 , J:156940 )

• at P1 in mutants with complete recombination synostosis with osteoid deposition is seen (J:101174)

• at P0, mice exhibit variation in the pattern and degree of coronal suture closure compared with wild-type mice (J:156940)

• mice exhibit unilateral or bilateral coronal suture synostosis unlike wild-type mice (J:156940)

premature lambdoid suture closure ( J:101174 )

• at P1 in mutants with complete recombination synostosis with osteoid deposition is seen

growth/size/body

abnormal nasal bone morphology ( J:101174 )

• dysmorphology of the nasal bones is seen in mutants with only partial recombination at 10 months of age

small face ( J:101174 )

• structures of the face are about 40-50% smaller in mutants with only partial recombination at 10 months of age

abnormal palate morphology ( J:101174 )

• malformations of the palate are seen in all mutants

abnormal head shape ( J:101174 )

• in mutants with only partial recombination at 10 months of age head shape is abnormal

shortened head ( J:101174 )

• in mutants with only partial recombination at 10 months of age skull width is more affected than skull length resulting in a brachycephalic skull shape

meteorism ( J:101174 )

• aerophagia with mild distension of the stomach and intestine is seen in mutants with complete recombination

decreased birth weight ( J:101174 )

• at birth in mutants with complete recombination body weight is about 83% that of wild-type littermates

decreased body weight ( J:101174 )

• in mutants with only partial recombination at 10 months of age body weight is 29% that of wild-type littermates

decreased body length ( J:101174 )

• in mutants with only partial recombination at 10 months of age body length is 68% that of wild-type littermates

cardiovascular system

dilated heart atrium ( J:101174 )

• mild dilation of the atria is seen in mutants with complete recombination

abnormal vasodilation ( J:101174 )

• mild dilation of the great vessels at the base of the heart is seen in mutants with complete recombination

immune system

abnormal thymus morphology ( J:101174 )

• diffuse lymphoid necrosis and apoptosis of variable severity is seen in mutants with complete recombination

decreased osteoclast cell number ( J:101174 )

• in mutants with complete recombination, a decrease in osteoclast numbers is seen at the chondro-osseous junction in long bones

bronchiolectasis ( J:101174 )

• multifocal and acute bronchiolectasis with mild dilation of the bronchioles are seen in mutants with complete recombination

nervous system

abnormal brain morphology ( J:156940 )

• 4 of 10 mice exhibit severe brain asymmetry unlike in wild-type mice

• 1 of 10 mice exhibit mild brain asymmetry unlike in wild-type mice

• rostrocaudal brain length is decreased compared to in wild-type mice

hydrocephaly ( J:101174 )

• mild hydroencephaly with enlarged ventricles is present in mutants with complete recombination

increased brain size ( J:156940 )

enlarged fourth ventricle ( J:156940 )

• in 2 of 10 mice

abnormal cerebral hemisphere morphology ( J:156940 )

• cerebral height is increased compared to in wild-type mice

• mice exhibit cerebral asymmetry to varying degrees compared with wild-type mice

abnormal corpus callosum morphology ( J:156940 )

• arched in 2 of 10 mice

craniofacial

abnormal craniofacial bone morphology ( J:101174 )

abnormal cranial suture morphology ( J:101174 )

• in mutants with only partial recombination at 10 months of age multiple interfrontal suture defects are seen and the fronto-premaxillary, premaxillary-maxillary, and nasal-frontal sutures are obliterated

wide metopic suture ( J:101174 )

• at P1 in mutants with complete recombination the space between the osteogenic fronts is increased

• at E18.5 in mutants with complete recombination increased numbers of proliferating cells are seen between the osteogenic fronts and no differentiating osteoblasts are found between the osteogenic fronts unlike in wild-type mice

abnormal sagittal suture morphology ( J:101174 )

• at E16.5 and E18.5 in mutants with complete recombination ectopic cartilage is found along all (E16.5) or over half (E18.5) of the length of the suture

• at E18.5 in mutants with complete recombination the space between the osteogenic fronts is decreased and at P1 the osteogenic fronts are very close and osteoid is deposited between the fronts prior to synostosis

• at E18.5 and P1 in mutants with complete recombination twice as many proliferating cells are seen and some of these cells are abnormally distributed in the space between the osteogenic fronts

• at E18.5 in mutants with complete recombination, markers of osteoblast differentiation are seen in cells from the edge of the bone plates into the mid-sutural area of the saggital suture where preosteoblasts are not normally found

abnormal basicranium morphology ( J:101174 )

• increased cartilage is found on the basicranium at birth in mutants with complete recombination

• structures of the basicranium are about 30-40% smaller in mutants with only partial recombination at 10 months of age

decreased cranium height ( J:101174 )

• skull height is significantly reduced in mutants with complete recombination

decreased cranium length ( J:101174 )

• skull length is significantly reduced in mutants with complete recombination

small cranium ( J:101174 )

• skull length and height are significantly reduced in mutants with complete recombination

• in mutants with only partial recombination at 10 months of age skull width is more affected than skull length resulting in a brachycephalic skull shape

abnormal interparietal bone morphology ( J:101174 )

• the interparietal bone is compressed superiorly at the lambdoid suture in mutants with only partial recombination at 10 months of age

parietal bossing ( J:101174 )

• the parietal bones have an obvious superior bulge in mutants with only partial recombination at 10 months of age

abnormal zygomatic arch morphology ( J:101174 )

• the temporal process of the zygomatic bone is fused to the zygomatic process of the temporal bone in mutants with complete recombination

small neurocranium ( J:101174 )

• structures of the neurocranium are about 30-40% smaller in mutants with only partial recombination at 10 months of age

abnormal mandible morphology ( J:101174 )

abnormal mandibular angle morphology ( J:101174 )

• dysmorphic angular process in mutants with only partial recombination at 10 months of age

small mandible ( J:101174 )

• the mandible is very small in mutants with only partial recombination at 10 months of age

abnormal maxillary frontal process morphology ( J:101174 )

• the frontal process of the maxilla has an abnormally large sinus and bowing of the medial wall in mutants with only partial recombination at 10 months of age

abnormal maxillary zygomatic process morphology ( J:101174 )

• the zygomatic process is bowed more laterally in mutants with only partial recombination at 10 months of age

short maxilla ( J:101174 )

• seen in mutants with complete recombination

abnormal nasal bone morphology ( J:101174 )

• dysmorphology of the nasal bones is seen in mutants with only partial recombination at 10 months of age

small face ( J:101174 )

• structures of the face are about 40-50% smaller in mutants with only partial recombination at 10 months of age

abnormal palate morphology ( J:101174 )

• malformations of the palate are seen in all mutants

abnormal head shape ( J:101174 )

• in mutants with only partial recombination at 10 months of age head shape is abnormal

shortened head ( J:101174 )

• in mutants with only partial recombination at 10 months of age skull width is more affected than skull length resulting in a brachycephalic skull shape

hematopoietic system

abnormal thymus morphology ( J:101174 )

• diffuse lymphoid necrosis and apoptosis of variable severity is seen in mutants with complete recombination

decreased osteoclast cell number ( J:101174 )

• in mutants with complete recombination, a decrease in osteoclast numbers is seen at the chondro-osseous junction in long bones

digestive/alimentary system

abnormal palate morphology ( J:101174 )

• malformations of the palate are seen in all mutants

aerophagia ( J:101174 )

• aerophagia with mild distension of the stomach and intestine is seen in mutants with complete recombination

meteorism ( J:101174 )

• aerophagia with mild distension of the stomach and intestine is seen in mutants with complete recombination

muscle

abnormal vasodilation ( J:101174 )

• mild dilation of the great vessels at the base of the heart is seen in mutants with complete recombination

homeostasis/metabolism

pulmonary alveolar proteinosis ( J:101174 )

• presence of proteinaceous fluid in the alveoli is observed

cellular

abnormal osteoblast differentiation ( J:101174 )

• at E18.5 in mutants with complete recombination, markers of osteoblast differentiation are seen in cells from the edge of the bone plates into the mid-sutural area of the saggital suture where preosteoblasts are not normally found

• at E18.5 in mutants with complete recombination no differentiating osteoblasts are found between the osteogenic fronts unlike in wild-type mice

endocrine/exocrine glands

abnormal thymus morphology ( J:101174 )

• diffuse lymphoid necrosis and apoptosis of variable severity is seen in mutants with complete recombination

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acrocephalosyndactylia		DOID:12960	OMIM:101200	J:101174 , J:156940

Genotype
MGI:5705483

cn15

• Allelic Composition: Pelo^tm2Imad/Pelo^tm2Imad; Tg(EIIa-cre)C5379Lmgd/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/N

mortality/aging

embryonic lethality, complete penetrance ( J:228122 )

• genotyping more than 100 embryos from intercrosses of EIIa-cre hemizyogus floxed heterozygotes found no null homozygotes at E8.5 indicating complete embryonic lethality of post-cre null allele

Genotype
MGI:3814198

cn16

• Allelic Composition: Piga^tm1Bsl/Piga⁺; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S1/Sv * FVB/NJ

mortality/aging

perinatal lethality, incomplete penetrance ( J:75506 )

♀ • increased perinatal lethality

hematopoietic system

abnormal definitive hematopoiesis ( J:75506 )

♀ • high level of blood cells lacking glycosylphosphatidylinositol anchors

abnormal erythrocyte morphology ( J:75506 )

♀ • level of RBC lacking glycosylphosphatidylinositol anchors highest at birth (up to 53%) and declining over 4 weeks to around 4%

reticulocytosis ( J:75506 )

♀ • elevated numbers of reticulocytes

abnormal erythrocyte physiology ( J:75506 )

♀ • RBC half life only 50% of normal

increased erythrocyte osmotic fragility ( J:75506 )

♀ • increased susceptibility to lytic activity of activated complement

craniofacial

abnormal facial morphology ( J:56055 )

♀ • orofacial abnormalities when cre recombination levels are highest

cleft palate ( J:56055 )

♀ • when cre recombination levels are highest

behavior/neurological

abnormal suckling behavior ( J:56055 )

♀ • unable to suckle when cre recombination levels are highest

digestive/alimentary system

cleft palate ( J:56055 )

♀ • when cre recombination levels are highest

growth/size/body

abnormal facial morphology ( J:56055 )

♀ • orofacial abnormalities when cre recombination levels are highest

cleft palate ( J:56055 )

♀ • when cre recombination levels are highest

Genotype
MGI:5292118

cn17

• Allelic Composition: Tg(EIIa-cre)C5379Lmgd/0; Tg(Rnu6-RNAi:Bccip)4Zshn/0; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * FVB/N

mortality/aging

embryonic lethality ( J:176115 )

• Trp53 deficiency does not result in significant rescue of the embryonic lethality seen in Bccip deficiency; ratio of viable double transgenic to wild-type offspring is not increased in the Trp53-null or heterozygous background

Genotype
MGI:3709752

cn18

• Allelic Composition: Drd1^tm2Jcd/Drd1⁺; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * CD-1 * FVB/N

mortality/aging

postnatal lethality, complete penetrance ( J:120582 )

• at P2 mice have a small or absent milk spot and most die during the first postnatal week with some surviving to P19

nervous system

decreased brain size ( J:120582 )

• at P4

decreased brain weight ( J:120582 )

• at P4

abnormal forebrain morphology ( J:120582 )

• some distortion in the normal relationship of the forebrain and hippocampus

• islands of Calleja are absent

decreased forebrain size ( J:120582 )

decreased forebrain volume ( J:120582 )

• forebrain is smaller and volumetrically reduced by about 40% in the striatum with no change in cortical thickness

abnormal striatum morphology ( J:120582 )

• hypercellular stratum with frequent condensed nuclear bodies

• mice have an increase apoptotic striatum cells

abnormal hippocampus morphology ( J:120582 )

• some distortion in the normal relationship of the forebrain and hippocampus

• hippocampus is displayed anteriorly

gliosis ( J:120582 )

• increase in reactive gliosis in the lateral stratum and along the corpus callosum

abnormal nervous system physiology ( J:120582 )

• neuropeptides substance P and dynorphin are absent

myoclonus ( J:120582 )

• falls are more myoclonic jerks than ataxia and are sometimes locomotor-activated

• at less than P6, all mice exhibit myoclonic jerks compared to 2 of 11 normal mice

behavior/neurological

impaired righting response ( J:120582 )

• mice fail to right after spontaneous falls

dystonia ( J:120582 )

• mice display peripheral dystonia that contributes to some falls

impaired balance ( J:120582 )

• frequent falls at P2 some due to dystonia while other falls are erratic, violent, intrusive and associated with attempted movement or tactile stimulation

• falls are more myoclonic jerks than ataxia

abnormal posture ( J:120582 )

• mice have an abnormal posture when at rest

bradykinesia ( J:120582 )

myoclonus ( J:120582 )

• falls are more myoclonic jerks than ataxia and are sometimes locomotor-activated

• at less than P6, all mice exhibit myoclonic jerks compared to 2 of 11 normal mice

muscle

dystonia ( J:120582 )

• mice display peripheral dystonia that contributes to some falls

myoclonus ( J:120582 )

• falls are more myoclonic jerks than ataxia and are sometimes locomotor-activated

• at less than P6, all mice exhibit myoclonic jerks compared to 2 of 11 normal mice

respiratory system

decreased pulmonary respiratory rate ( J:120582 )

• at P2 mice exhibit periodic breathing that is resolved in older pups

Genotype
MGI:5435562

cn19

• Allelic Composition: Porcn^tm1.1Vdv/Y; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S4/SvJaeSor * 129S5/SvEvBrd * C57BL/6J * FVB/N

mortality/aging

prenatal lethality, incomplete penetrance ( J:186934 )

♂ • out of 13 litters only 3 males were recovered and these had a low level of mosaicism

integument

abnormal hair growth ( J:186934 )

♂ • decreased hair growth in survivors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
focal dermal hypoplasia		DOID:2120	OMIM:305600	J:186934

Genotype
MGI:5435561

cn20

• Allelic Composition: Porcn^tm1.1Vdv/Porcn⁺; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S4/SvJaeSor * 129S5/SvEvBrd * C57BL/6J * FVB/N

mortality/aging

prenatal lethality, incomplete penetrance ( J:186934 )

♀ • out of 13 litters only 3 males were recovered and these had a low level of mosaicism

integument

abnormal hair growth ( J:186934 )

♀ • decreased hair growth in survivors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
focal dermal hypoplasia		DOID:2120	OMIM:305600	J:186934

Genotype
MGI:4838160

cn21

• Allelic Composition: Ccn2^tm2Mae/Ccn2⁺; Tg(EIIa-cre)C5379Lmgd/?
• Genetic Background: involves: 129S6/SvEvTac

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:165111 )

• Background Sensitivity: no heterozygous embryos after E12.5

embryo

abnormal pharyngeal arch development ( J:165111 )

• pharyngeal arches remain open

embryonic growth retardation ( J:165111 )

• small and embryonic development is delayed at E10.5

cardiovascular system

abnormal vasculogenesis ( J:165111 )

• less visible vasculature

craniofacial

abnormal facial morphology ( J:165111 )

• shortened face in mice surviving to adulthood (4/81)

small ears ( J:165111 )

• in mice surviving to adulthood (4/81)

limbs/digits/tail

short tail ( J:165111 )

• in mice surviving to adulthood (4/81)

kinked tail ( J:165111 )

• in mice surviving to adulthood (4/81)

skeleton

abnormal bone structure ( J:165111 )

• smaller bone area in mice surviving to adulthood (4/81)

decreased bone mineral content ( J:165111 )

• in mice surviving to adulthood (4/81)

growth/size/body

abnormal facial morphology ( J:165111 )

• shortened face in mice surviving to adulthood (4/81)

small ears ( J:165111 )

• in mice surviving to adulthood (4/81)

embryonic growth retardation ( J:165111 )

• small and embryonic development is delayed at E10.5

decreased lean body mass ( J:165111 )

• in mice surviving to adulthood (4/81)

hearing/vestibular/ear

small ears ( J:165111 )

• in mice surviving to adulthood (4/81)

Genotype
MGI:5313418

cn22

• Allelic Composition: Tgfb3^tm1Moaz/Tgfb3^tm1.1Moaz; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss * C57BL/6J * FVB/N

mortality/aging

neonatal lethality, complete penetrance ( J:181226 )

• although born at the expected ratio, homozyotes gasp, suckle poorly and die

respiratory system

respiratory distress ( J:181226 )

• gasping after birth

behavior/neurological

absent gastric milk in neonates ( J:181226 )

• little or no milk in pups' stomachs

abnormal suckling behavior ( J:181226 )

• suckle poorly

craniofacial

cleft palate ( J:181226 )

• complete or partial cleft palate in all E18.5 embryos and in new born pups

complete cleft palate ( J:181226 )

digestive/alimentary system

cleft palate ( J:181226 )

• complete or partial cleft palate in all E18.5 embryos and in new born pups

complete cleft palate ( J:181226 )

growth/size/body

cleft palate ( J:181226 )

• complete or partial cleft palate in all E18.5 embryos and in new born pups

complete cleft palate ( J:181226 )

Genotype
MGI:3615451

cn23

• Allelic Composition: Cbfb^tm1Lhc/Cbfb⁺; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB/N

mortality/aging

embryonic lethality, complete penetrance ( J:105040 )

• embryos die by midgestation

hematopoietic system

impaired hematopoiesis ( J:105040 )

• embryos display hematopoeitic deficiency

Genotype
MGI:4838158

cn24

• Allelic Composition: Ccn2^tm2Mae/Ccn2⁺; Tg(EIIa-cre)C5379Lmgd/?
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB/N

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:165111 )

• Background Sensitivity: no heterozygous embryos after E14.5

embryo

embryonic growth retardation ( J:165111 )

• small and embryonic development is delayed

decreased embryo size ( J:165111 )

cardiovascular system

abnormal vasculogenesis ( J:165111 )

• poor vascularization at E13.5-14.5

vision/eye

abnormal eye development ( J:165111 )

• eye is less developed at E13.5-14.5

craniofacial

short face ( J:165111 )

• shortened face in mice surviving to adulthood (4/81)

facial cleft ( J:165111 )

lateral facial cleft ( J:165111 )

• at E13.5-14.5

midline facial cleft ( J:165111 )

• at E13.5-14.5

small ears ( J:165111 )

• in mice surviving to adulthood (4/81)

limbs/digits/tail

short tail ( J:165111 )

• in mice surviving to adulthood (4/81)

kinked tail ( J:165111 )

• in mice surviving to adulthood (4/81)

skeleton

abnormal bone structure ( J:165111 )

• smaller bone area in mice surviving to adulthood (4/81)

decreased bone mineral content ( J:165111 )

• in mice surviving to adulthood (4/81)

growth/size/body

short face ( J:165111 )

• shortened face in mice surviving to adulthood (4/81)

facial cleft ( J:165111 )

lateral facial cleft ( J:165111 )

• at E13.5-14.5

midline facial cleft ( J:165111 )

• at E13.5-14.5

small ears ( J:165111 )

• in mice surviving to adulthood (4/81)

embryonic growth retardation ( J:165111 )

• small and embryonic development is delayed

decreased embryo size ( J:165111 )

decreased lean body mass ( J:165111 )

• in mice surviving to adulthood (4/81)

hearing/vestibular/ear

small ears ( J:165111 )

• in mice surviving to adulthood (4/81)

Genotype
MGI:5827939

cn25

• Allelic Composition: Sox11^tm1.1Gan/Sox11^tm1.1Gan; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB/N

Sox11^tm1.1Gan/Sox11^tm1.1Gan Tg(EIIa-cre)C5379Lmgd/0 mutants display cleft palate with retardation to palatal shelf elevation

craniofacial

abnormal craniofacial morphology ( J:232434 )

• 100% penetrance of craniofacial malformations

small Meckel's cartilage ( J:232434 )

• reduction in Meckel cartilage size at E13.5

abnormal mandible morphology ( J:232434 )

• the mandible shows decreased proliferation in mesenchymal cells in and around the Meckel cartilage at E13.5

mandible hypoplasia ( J:232434 )

• mandible is narrow and small

short mandible ( J:232434 )

• reduction in mandibular length at E13.5

abnormal palatal mesenchymal cell proliferation ( J:232434 )

• a 25% reduction in palatal mesenchyme is seen at E13.5

• mesenchymal cell proliferation is reduced in the proximal bend region of the palatal shelf at E13.5

abnormal secondary palate development ( J:232434 )

• delay in elevation of palatal shelves resulting in retardation of palatal shelf formation

• a 25% reduction in palatal mesenchyme is seen at E13.5

• a 19% reduction in palatal epithelial cells is seen at E13.5

• proliferation of both epithelial and mesenchymal cells in the proximal bend region of the palatal shelf is reduced at E13.5

• however, the fusion mechanism of palatal shelves is not disrupted; bilateral palatal shelves grown in culture on Nucleopore filters show complete fusion

decreased palatal shelf size ( J:232434 )

• the palatal shelves become regressed at the proximal portion, resulting in reduction in the size of the palatal shelves at E15.5

cleft upper lip ( J:232434 )

• cleft lip in 70% of mutants

cleft secondary palate ( J:232434 )

• complete clefting of the secondary palate

delayed palatal shelf elevation ( J:232434 )

• the bilateral palatal shelves of E14.5 embryos fail to elevate and remain at the vertical position at E14.5 and E15.5 although occasional elevation of one or both sides of the palatal shelves occurs in later stages

• however, initial downward growth of palatal shelves occurs normally at E11.5, E12.5, and E13.5

• in vitro organ culture of E13.5 head with mandible or tongue removed in roller bottles show that palatal shelves are able to elevate after 24 hours in rolling culture

abnormal tongue position ( J:232434 )

• tongue position remains heightened during palatal elevation by E14.5 along the anterior-posterior axis causing physical retardation of palatal elevation

digestive/alimentary system

abnormal palatal mesenchymal cell proliferation ( J:232434 )

• a 25% reduction in palatal mesenchyme is seen at E13.5

• mesenchymal cell proliferation is reduced in the proximal bend region of the palatal shelf at E13.5

abnormal secondary palate development ( J:232434 )

• delay in elevation of palatal shelves resulting in retardation of palatal shelf formation

• a 25% reduction in palatal mesenchyme is seen at E13.5

• a 19% reduction in palatal epithelial cells is seen at E13.5

• proliferation of both epithelial and mesenchymal cells in the proximal bend region of the palatal shelf is reduced at E13.5

• however, the fusion mechanism of palatal shelves is not disrupted; bilateral palatal shelves grown in culture on Nucleopore filters show complete fusion

decreased palatal shelf size ( J:232434 )

• the palatal shelves become regressed at the proximal portion, resulting in reduction in the size of the palatal shelves at E15.5

cleft secondary palate ( J:232434 )

• complete clefting of the secondary palate

delayed palatal shelf elevation ( J:232434 )

• the bilateral palatal shelves of E14.5 embryos fail to elevate and remain at the vertical position at E14.5 and E15.5 although occasional elevation of one or both sides of the palatal shelves occurs in later stages

• however, initial downward growth of palatal shelves occurs normally at E11.5, E12.5, and E13.5

• in vitro organ culture of E13.5 head with mandible or tongue removed in roller bottles show that palatal shelves are able to elevate after 24 hours in rolling culture

abnormal tongue position ( J:232434 )

• tongue position remains heightened during palatal elevation by E14.5 along the anterior-posterior axis causing physical retardation of palatal elevation

growth/size/body

abnormal palatal mesenchymal cell proliferation ( J:232434 )

• a 25% reduction in palatal mesenchyme is seen at E13.5

• mesenchymal cell proliferation is reduced in the proximal bend region of the palatal shelf at E13.5

abnormal secondary palate development ( J:232434 )

• delay in elevation of palatal shelves resulting in retardation of palatal shelf formation

• a 25% reduction in palatal mesenchyme is seen at E13.5

• a 19% reduction in palatal epithelial cells is seen at E13.5

• proliferation of both epithelial and mesenchymal cells in the proximal bend region of the palatal shelf is reduced at E13.5

• however, the fusion mechanism of palatal shelves is not disrupted; bilateral palatal shelves grown in culture on Nucleopore filters show complete fusion

decreased palatal shelf size ( J:232434 )

• the palatal shelves become regressed at the proximal portion, resulting in reduction in the size of the palatal shelves at E15.5

cleft upper lip ( J:232434 )

• cleft lip in 70% of mutants

cleft secondary palate ( J:232434 )

• complete clefting of the secondary palate

delayed palatal shelf elevation ( J:232434 )

• the bilateral palatal shelves of E14.5 embryos fail to elevate and remain at the vertical position at E14.5 and E15.5 although occasional elevation of one or both sides of the palatal shelves occurs in later stages

• however, initial downward growth of palatal shelves occurs normally at E11.5, E12.5, and E13.5

• in vitro organ culture of E13.5 head with mandible or tongue removed in roller bottles show that palatal shelves are able to elevate after 24 hours in rolling culture

abnormal tongue position ( J:232434 )

• tongue position remains heightened during palatal elevation by E14.5 along the anterior-posterior axis causing physical retardation of palatal elevation

skeleton

small Meckel's cartilage ( J:232434 )

• reduction in Meckel cartilage size at E13.5

abnormal mandible morphology ( J:232434 )

• the mandible shows decreased proliferation in mesenchymal cells in and around the Meckel cartilage at E13.5

mandible hypoplasia ( J:232434 )

• mandible is narrow and small

short mandible ( J:232434 )

• reduction in mandibular length at E13.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Weissenbacher-Zweymuller syndrome		DOID:4258	OMIM:261800	J:232434

Genotype
MGI:5446521

cn26

• Allelic Composition: Zfhx3^tm1.1Jtd/Zfhx3⁺; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB/N * SJL

mortality/aging

preweaning lethality, incomplete penetrance ( J:189563 )

• half of mice die by weaning

Genotype
MGI:5790180

cn27

• Allelic Composition: Fgfr2^tm2Cxd/Fgfr2⁺; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * FVB/N

craniofacial

wide intermaxillary suture ( J:228708 )

• widening of the intermaxillary suture

abnormal presphenoid bone morphology ( J:228708 )

• increase in cartilaginous appearance of the presphenoid bone indicating reduced ossification of this bone

abnormal zygomatic arch morphology ( J:228708 )

• fusion of the zygomatic arch at P0

short nasal bone ( J:228708 )

• foreshortening of the nasal bone

abnormal palatine bone morphology ( J:228708 )

• severe palatal bone dysplasia at P0 associated with a widening of the intermaxillary suture

• dysplasia of the palatine bone involves anterior curvature of the vertical processes and an overall porous appearance

domed cranium ( J:228708 )

midface hypoplasia ( J:228708 )

growth/size/body

short nasal bone ( J:228708 )

• foreshortening of the nasal bone

midface hypoplasia ( J:228708 )

skeleton

wide intermaxillary suture ( J:228708 )

• widening of the intermaxillary suture

abnormal presphenoid bone morphology ( J:228708 )

• increase in cartilaginous appearance of the presphenoid bone indicating reduced ossification of this bone

abnormal zygomatic arch morphology ( J:228708 )

• fusion of the zygomatic arch at P0

short nasal bone ( J:228708 )

• foreshortening of the nasal bone

abnormal palatine bone morphology ( J:228708 )

• severe palatal bone dysplasia at P0 associated with a widening of the intermaxillary suture

• dysplasia of the palatine bone involves anterior curvature of the vertical processes and an overall porous appearance

domed cranium ( J:228708 )

abnormal trabecular bone morphology ( J:228708 )

• poor cancellous bone formation of the cranial base

premature coronal suture closure ( J:228708 )

• fusion of the coronal suture at P0

premature facial suture closure ( J:228708 )

• facial suture synostosis at P0, with fusion of the premaxillary-maxillary, nasal-frontal, and maxillary-palatine sutures

premature maxillary-premaxillary suture closure ( J:228708 )

• fusion of the premaxillary-maxillary suture at P0

premature palatomaxillary suture closure ( J:228708 )

• fusion of the maxillary-palatine suture at P0

premature frontonasal suture closure ( J:228708 )

• fusion of the nasal-frontal suture at P0

respiratory system

short nasal bone ( J:228708 )

• foreshortening of the nasal bone

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acrocephalosyndactylia		DOID:12960	OMIM:101200	J:228708

Genotype
MGI:5902066

cn28

• Allelic Composition: Del(XMagea1-Magea6)1Nju/Y; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * FVB/N

cellular

oligozoospermia ( J:240206 )

♂ • overall sperm count normal at P30 and 5 months

♂ • decrease in the testicular sperm reserve at 2 months

increased cellular sensitivity to DNA damaging agents ( J:240206 )

♂ • increased proportions of apoptotic and dead spermatocytes in the seminiferous tubules 24h after injection with DNA-damaging agent N-ethyl-N-nitrosourea (ENU) at 3 months

♂ • higher levels of Trp53 protein in the testes 3 hours after ENU administration

♂ • higher level of Ser15-phosphorylation of Trp53 in the testes 6 hours after ENU treatment

♂ • increased level of apoptosis marker Bax in testes 6 hours after ENU treatment

increased male germ cell apoptosis ( J:240206 )

♂ • increased apoptosis in spermatocytes at P12

endocrine/exocrine glands

small seminiferous tubules ( J:240206 )

♂ • reduction in the area, diameter and perimeter of the seminiferous tubules at 3 months

decreased testis weight ( J:240206 )

♂ • P30 and earlier

♂ • average testicular mass to body mass ratio was 16.6% lower from 2 months

reproductive system

oligozoospermia ( J:240206 )

♂ • overall sperm count normal at P30 and 5 months

♂ • decrease in the testicular sperm reserve at 2 months

increased male germ cell apoptosis ( J:240206 )

♂ • increased apoptosis in spermatocytes at P12

small seminiferous tubules ( J:240206 )

♂ • reduction in the area, diameter and perimeter of the seminiferous tubules at 3 months

decreased testis weight ( J:240206 )

♂ • P30 and earlier

♂ • average testicular mass to body mass ratio was 16.6% lower from 2 months

Genotype
MGI:3834095

cn29

• Allelic Composition: Egfr^tm1Dwt/Egfr^tm1Dwt; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * FVB/N

Placenta abnormalities in Egfr^tm1Dwt/Egfr^tm1Dwt Tg(EIIa-cre)C5379Lmgd/0 mice

embryo

decreased embryo size ( J:145161 )

• at mid-gestation

abnormal spongiotrophoblast layer morphology ( J:145161 )

• mice exhibit similar defects to those observed in Egfr^tm1Mag homozygotes

• the numbers of trophoblasts and glycogen cells in the spongiotrophoblast is moderately to severely reduced compared to in wild-type mice

abnormal placenta labyrinth morphology ( J:145161 )

• mice exhibit similar defects to those observed in Egfr^tm1Mag homozygotes

• the labyrinth is reduced in size and disorganized compared to in wild-type mice

placental labyrinth hypoplasia ( J:145161 )

growth/size/body

decreased embryo size ( J:145161 )

• at mid-gestation

Genotype
MGI:3691285

cn30

• Allelic Composition: Erbb3^tm1Squ/Erbb3^tm1Squ; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:114524 )

• normal numbers of homozygous embryos are found at E12.5 but number of viable embryos is severely reduced at E13.5

nervous system

absent Schwann cells ( J:114524 )

• there is a lack of Schwann cells and Schwann cell precursors in DRGs

abnormal dorsal root ganglion morphology ( J:114524 )

• there is a lack of Schwann cells and Schwann cell precursors in DRGs

cardiovascular system

abnormal atrioventricular valve morphology ( J:114524 )

• mutants exhibit defects in the atrioventricular valves

Genotype
MGI:3604078

cn31

• Allelic Composition: Fgfr2^tm2Cxd/Fgfr2⁺; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

mortality/aging

postnatal lethality, incomplete penetrance ( J:101385 )

• mutants with severe cranial abnormalities die within 20 days of birth, less severely affected mutants survive to adulthood

growth/size/body

malocclusion ( J:101385 )

midface hypoplasia ( J:101385 )

• midface hypoplasia

decreased embryo size ( J:101385 )

• severely affected mutants are very small compared to wild-type mice, less severely affected mutants are 70-80% of the size of wild-type littermates

skeleton

abnormal cranium morphology ( J:101385 )

• some adults have asymmetrical skulls; however no obvious hand/foot abnormalities are seen

abnormal cranial suture morphology ( J:101385 )

• at P1 and P8 increased apoptosis is seen with the highest levels seen in the parietal and frontal bones; however no significant difference in osteoblast proliferation (at E16.5, E18.5, P1, P5, and P8) or differentiation (at E18.5, P1, and P18) is seen in the sutures

abnormal sagittal suture morphology ( J:101385 )

• development of the sagittal suture is slightly delayed

decreased cranium height ( J:101385 )

• significant shortening of the anterior-posterior axis

abnormal neurocranium morphology ( J:101385 )

• calvarial bone formation is decreased

thin frontal bone ( J:101385 )

• the frontal bone is thinner and at P1 and P8 increased apoptosis is seen

thin parietal bone ( J:101385 )

• the parietal bone is thinner and at P1 and P8 increased apoptosis is seen

short presphenoid bone ( J:101385 )

• the presphenoid bone is significantly shorter

malocclusion ( J:101385 )

domed cranium ( J:101385 )

abnormal long bone epiphyseal plate proliferative zone ( J:101385 )

• after P10 some mutants have slightly shorter columns of proliferating chondrocytes

premature cranial suture closure ( J:101385 )

• craniosynostosis is most pronounced in the coronal suture

premature coronal suture closure ( J:101385 )

• premature closure of the coronal suture is first seen around E18.5 with more significant overlap between the osteogenic fronts developing over time and fewer mesenchymal cells are found in the coronal suture at birth

vision/eye

ocular hypertelorism ( J:101385 )

reproductive system

female infertility ( J:101385 )

♀ • all surviving females are sterile

reduced male fertility ( J:101385 )

♂ • only 1 male generated 2 litters when mated with a wild-type female

craniofacial

abnormal craniofacial morphology ( J:101385 )

• cranial abnormalities vary in severity and the severely affected mutants die postnatally

abnormal cranium morphology ( J:101385 )

• some adults have asymmetrical skulls; however no obvious hand/foot abnormalities are seen

abnormal cranial suture morphology ( J:101385 )

• at P1 and P8 increased apoptosis is seen with the highest levels seen in the parietal and frontal bones; however no significant difference in osteoblast proliferation (at E16.5, E18.5, P1, P5, and P8) or differentiation (at E18.5, P1, and P18) is seen in the sutures

abnormal sagittal suture morphology ( J:101385 )

• development of the sagittal suture is slightly delayed

decreased cranium height ( J:101385 )

• significant shortening of the anterior-posterior axis

abnormal neurocranium morphology ( J:101385 )

• calvarial bone formation is decreased

thin frontal bone ( J:101385 )

• the frontal bone is thinner and at P1 and P8 increased apoptosis is seen

thin parietal bone ( J:101385 )

• the parietal bone is thinner and at P1 and P8 increased apoptosis is seen

short presphenoid bone ( J:101385 )

• the presphenoid bone is significantly shorter

malocclusion ( J:101385 )

domed cranium ( J:101385 )

midface hypoplasia ( J:101385 )

• midface hypoplasia

embryo

decreased embryo size ( J:101385 )

• severely affected mutants are very small compared to wild-type mice, less severely affected mutants are 70-80% of the size of wild-type littermates

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acrocephalosyndactylia		DOID:12960	OMIM:101200	J:101385

Genotype
MGI:3845015

cn32

• Allelic Composition: Ptpn11^tm6Bgn/Ptpn11⁺; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

mortality/aging

preweaning lethality, complete penetrance ( J:148430 )

• no viable recombinants are found

Genotype
MGI:3580087

cn33

• Allelic Composition: Arhgap6/Hccs/Mid1^tm1Hzo/Arhgap6/Hccs/Mid1^tm1Hzo; Tg(EIIa-cre)C5379Lmgd/?
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB/N

mortality/aging

prenatal lethality, complete penetrance ( J:80528 )

♀ • 15 of 21 embryos abnormal at E9.5 and E10.5

♀ • mosaic animals were present and were healthy and fertile

♀ • no homozygous mice born

embryo

abnormal embryo development ( J:80528 )

♀ • many embryos undergoing resorption by E9.5-E10.5

abnormal gastrulation ( J:80528 )

♀ • gastrulation defects

embryonic growth retardation ( J:80528 )

♀

growth/size/body

embryonic growth retardation ( J:80528 )

♀

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
microphthalmia		DOID:10629		J:80528

Genotype
MGI:3580088

cn34

• Allelic Composition: Arhgap6/Hccs/Mid1^tm1Hzo/Y; Tg(EIIa-cre)C5379Lmgd/?
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB/N

mortality/aging

prenatal lethality, complete penetrance ( J:80528 )

♂ • no hemizygous mice born

♂ • 15 of 21 embryos abnormal at E9.5 and E10.5

♂ • mosaic animals were present and were healthy and fertile

embryo

abnormal embryo development ( J:80528 )

♂ • many embryos undergoing resorption by E9.5-E10.5

abnormal gastrulation ( J:80528 )

♂ • gastrulation defects

embryonic growth retardation ( J:80528 )

♂

growth/size/body

embryonic growth retardation ( J:80528 )

♂

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
microphthalmia		DOID:10629		J:80528

Genotype
MGI:3580085

cn35

• Allelic Composition: Arhgap6/Hccs/Mid1^tm1Hzo/Arhgap6/Hccs/Mid1^tm1Hzo; Tg(EIIa-cre)C5379Lmgd/?
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB/N

mortality/aging

prenatal lethality, complete penetrance ( J:80528 )

♀ • 15 of 21 embryos abnormal at E9.5 and E10.5

♀ • mosaic animals were present and were healthy and fertile

♀ • no homozygous mice born

embryo

abnormal embryo development ( J:80528 )

♀ • many embryos undergoing resorption by E9.5-E10.5

abnormal gastrulation ( J:80528 )

♀ • gastrulation defects

embryonic growth retardation ( J:80528 )

♀

growth/size/body

embryonic growth retardation ( J:80528 )

♀

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
microphthalmia		DOID:10629		J:80528

Genotype
MGI:3580089

cn36

• Allelic Composition: Arhgap6/Hccs/Mid1^tm1Hzo/Arhgap6/Hccs/Mid1^tm1Hzo; Tg(EIIa-cre)C5379Lmgd/?
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB/N

mortality/aging

prenatal lethality, complete penetrance ( J:80528 )

♀ • no homozygous mice born

♀ • 15 of 21 embryos abnormal at E9.5 and E10.5

♀ • mosaic animals were present and were healthy and fertile

embryo

abnormal embryo development ( J:80528 )

♀ • many embryos undergoing resorption by E9.5-E10.5

abnormal gastrulation ( J:80528 )

♀ • gastrulation defects

embryonic growth retardation ( J:80528 )

♀

growth/size/body

embryonic growth retardation ( J:80528 )

♀

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
microphthalmia		DOID:10629		J:80528

Genotype
MGI:3580090

cn37

• Allelic Composition: Arhgap6/Hccs/Mid1^tm1Hzo/Y; Tg(EIIa-cre)C5379Lmgd/?
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB/N

mortality/aging

prenatal lethality, complete penetrance ( J:80528 )

♂ • no hemizygous mice born

♂ • 15 of 21 embryos abnormal at E9.5 and E10.5

♂ • mosaic animals were present and were healthy and fertile

embryo

abnormal embryo development ( J:80528 )

♂ • many embryos undergoing resorption by E9.5-E10.5

abnormal gastrulation ( J:80528 )

♂ • gastrulation defects

embryonic growth retardation ( J:80528 )

♂

growth/size/body

embryonic growth retardation ( J:80528 )

♂

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
microphthalmia		DOID:10629		J:80528

Genotype
MGI:3580091

cn38

• Allelic Composition: Arhgap6/Hccs/Mid1^tm1Hzo/Mid1⁺; Tg(EIIa-cre)C5379Lmgd/?
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB/N

mortality/aging

prenatal lethality, complete penetrance ( J:80528 )

♀ • no heterozygotes born

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
microphthalmia		DOID:10629		J:80528

Genotype
MGI:3580092

cn39

• Allelic Composition: Arhgap6/Hccs/Mid1^tm1Hzo/Hccs⁺; Tg(EIIa-cre)C5379Lmgd/?
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB/N

mortality/aging

prenatal lethality, complete penetrance ( J:80528 )

♀ • no heterozygotes born

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
microphthalmia		DOID:10629		J:80528

Genotype
MGI:3580093

cn40

• Allelic Composition: Arhgap6/Hccs/Mid1^tm1Hzo/Arhgap6⁺; Tg(EIIa-cre)C5379Lmgd/?
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB/N

mortality/aging

prenatal lethality, complete penetrance ( J:80528 )

♀ • no heterozygotes born

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
microphthalmia		DOID:10629		J:80528

Genotype
MGI:3580086

cn41

• Allelic Composition: Arhgap6/Hccs/Mid1^tm1Hzo/Y; Tg(EIIa-cre)C5379Lmgd/?
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB/N

mortality/aging

prenatal lethality, complete penetrance ( J:80528 )

♂ • no hemizygous mice born

♂ • 15 of 21 embryos abnormal at E9.5 and E10.5

♂ • mosaic animals were present and were healthy and fertile

embryo

abnormal embryo development ( J:80528 )

♂ • many embryos undergoing resorption by E9.5-E10.5

abnormal gastrulation ( J:80528 )

♂ • gastrulation defects

embryonic growth retardation ( J:80528 )

♂

growth/size/body

embryonic growth retardation ( J:80528 )

♂

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
microphthalmia		DOID:10629		J:80528

Genotype
MGI:3758885

cn42

• Allelic Composition: Inhba^tm1Zuk/Inhba^tm3Zuk; Tg(EIIa-cre)C5379Lmgd/?
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J * FVB/N

mortality/aging

neonatal lethality, complete penetrance ( J:125354 )

• mice die shortly after birth similar to Inhba^tm1Zuk homozygotes

Genotype
MGI:5141143

cn43

• Allelic Composition: Tet2^tm1.1Iaai/Tet2^tm1.1Iaai; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * FVB/N

normal phenotype

no abnormal phenotype detected ( J:174053 )

• mice are born with at the expected Mendelian ratio with normal growth and organ development

Genotype
MGI:4838404

cn44

• Allelic Composition: Wls^tm1.1Lan/Wls^tm1.1Lan; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S/SvEv * FVB/N * SJL

mortality/aging

embryonic lethality between implantation and somite formation, incomplete penetrance ( J:164701 )

• at E8.5, 9 of 10 embryos are in the process of being reabsorbed

embryo

embryonic growth arrest ( J:164701 )

• germline homozygotes appear arrested at E6, they do not progress past the egg cylinder stage, and by morphological criteria lack mesoderm

failure of primitive streak formation ( J:164701 )

Genotype
MGI:2176942

cn45

• Allelic Composition: Igf1^tm1Dlr/Igf1^tm1Dlr; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129/Sv * C57BL/6 * FVB/N

mortality/aging

perinatal lethality, incomplete penetrance ( J:49468 )

• some perinatal mortality but many survive

growth/size/body

slow postnatal weight gain ( J:49468 )

• 72% of control weight at 3 weeks of age, 68% at 6 weeks

fetal growth retardation ( J:49468 )

• fetus at E19 or E20 weighs only 69% as much as comparable controls

Genotype
MGI:6393909

cn46

• Allelic Composition: Rnu11^tm1.1Rank/Rnu11^tm1.1Rank; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129X1/SvJ * FVB/N

mortality/aging

embryonic lethality, complete penetrance ( J:266583 )

Genotype
MGI:5566808

cn47

• Allelic Composition: Serpina1a^tm1Amgh/Serpina1a^tm1Amgh; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129X1/SvJ * FVB/N

mortality/aging

embryonic lethality, complete penetrance ( J:208746 )

• mice die prior to E8.5

Genotype
MGI:5524228

cn48

• Allelic Composition: Fbxw7^tm2Iaai/Fbxw7⁺; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: C57BL/6 * FVB/N

embryo

embryo phenotype ( J:200006 )

N • mice do not develop developmental defects

neoplasm

neoplasm ( J:200006 )

N • mice do not develop tumors

Genotype
MGI:5292117

cn49

• Allelic Composition: Tg(EIIa-cre)C5379Lmgd/0; Tg(Rnu6-RNAi:Bccip)4Zshn/0
• Genetic Background: involves: C57BL/6 * FVB/N

mortality/aging

embryonic lethality during organogenesis ( J:176115 )

• lethality occurs before E11.5

growth/size/body

embryonic growth retardation ( J:176115 )

• significant delay and abnormal development is observed at E6.5, evidenced by abnormal mass of embryonic tissues relative to controls

• embryos at E7.5 and E8.5 show significant developmental retardation

embryo

increased embryonic tissue cell apoptosis ( J:176115 )

• elevated apoptosis is observed by E7.5 in mutant embryos, but at E6.5 there is little difference compared to controls

decreased inner cell mass proliferation ( J:176115 )

• growth of the inner cell mass is impaired in cultured mutant blastocysts compared to wild-type starting at culture day 3 (equivalent to E6.5 in vivo)

abnormal embryo development ( J:176115 )

abnormal mesoderm development ( J:176115 )

• no mesoderm differentiation is apparent at E7.5

embryonic growth arrest ( J:176115 )

• developmental arrest is observed at E11.5

embryonic growth retardation ( J:176115 )

• significant delay and abnormal development is observed at E6.5, evidenced by abnormal mass of embryonic tissues relative to controls

• embryos at E7.5 and E8.5 show significant developmental retardation

absent neural plate ( J:176115 )

• development of the neural plate is not evident at E8.5

absent notochord ( J:176115 )

• development of the notochord is not evident at E8.5

absent amniotic cavity ( J:176115 )

• amniotic cavity does not develop

cellular

increased embryonic tissue cell apoptosis ( J:176115 )

• elevated apoptosis is observed by E7.5 in mutant embryos, but at E6.5 there is little difference compared to controls

decreased cell proliferation ( J:176115 )

• the proliferation index of cells in embryonic tissues is slightly reduced at E6.5 relative to controls and reduction is significant by E7.5

decreased inner cell mass proliferation ( J:176115 )

• growth of the inner cell mass is impaired in cultured mutant blastocysts compared to wild-type starting at culture day 3 (equivalent to E6.5 in vivo)

nervous system

absent neural plate ( J:176115 )

• development of the neural plate is not evident at E8.5

reproductive system

decreased litter size ( J:176115 )

• litters are significantly smaller (5.1 pups/litter) than wild-type controls (10.3/litter)

• the number of double-positive transgenic offspring is greatly reduced, but some are viable; however, some of these animals were shown to have lost the RNAi cassette spontaneously

Genotype
MGI:4839527

cn50

• Allelic Composition: Epo^tm1Knni/Epo^tm1Knni; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: C57BL/6 * FVB/N

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:165479 )

• embryos died at 12.5 days post-coitum with severe defects in erythropoiesis

hematopoietic system

decreased erythrocyte cell number ( J:165479 )

• significant reduction in RBCs in the liver

Genotype
MGI:3712472

cn51

• Allelic Composition: Gna13^tm2.2Soff/Gna13^tm2.2Soff; Tg(EIIa-cre)C5379Lmgd/?
• Genetic Background: involves: FVB

homeostasis/metabolism

abnormal blood coagulation ( J:99597 )

• defects are indistinguishable from those in Gna12^tm1Citb Gna13^tm2.1Soff double homozygotes

abnormal platelet physiology ( J:99597 )

• defects are indistinguishable from those in Gna12^tm1Citb Gna13^tm2.1Soff double homozygotes

increased bleeding time ( J:99597 )

• defects are indistinguishable from those in Gna12^tm1Citb Gna13^tm2.1Soff double homozygotes

hematopoietic system

abnormal platelet physiology ( J:99597 )

• defects are indistinguishable from those in Gna12^tm1Citb Gna13^tm2.1Soff double homozygotes

Genotype
MGI:3714177

cn52

• Allelic Composition: Pawr^tm1Yshi/Pawr^tm1Yshi; Tg(EIIa-cre)C5379Lmgd/?
• Genetic Background: involves: FVB/N

normal phenotype

no abnormal phenotype detected ( J:108228 )

• mice are normal

Genotype
MGI:5308738

cn53

• Allelic Composition: Becn1^tm1Ebr/Becn1⁺; Tg(EIIa-cre)C5379Lmgd/?
• Genetic Background: involves: FVB/N

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:180916 )

• high level of death associated with heart and brain defects at embryonic days 11.5 and 12.5

cardiovascular system

abnormal heart development ( J:180916 )

• high level of death associated with heart defects at embryonic days 11.5 and 12.5

nervous system

abnormal brain development ( J:180916 )

• high level of death associated with brain defects at embryonic days 11.5 and 12.5

Genotype
MGI:6154152

cx54

• Allelic Composition: Tg(EIIa-cre)C5379Lmgd/?; Trip11^tm1.2Psmi/Trip11^tm1.2Psmi
• Genetic Background: involves: 129/Sv * C57BL/6 * FVB/N

cellular

abnormal endoplasmic reticulum morphology ( J:253969 )

• in E15.5 chondrocytes

craniofacial

maxilla hypoplasia ( J:253969 )

domed cranium ( J:253969 )

protruding tongue ( J:253969 )

digestive/alimentary system

protruding tongue ( J:253969 )

growth/size/body

protruding tongue ( J:253969 )

decreased body length ( J:253969 )

skeleton

maxilla hypoplasia ( J:253969 )

domed cranium ( J:253969 )

small thoracic cage ( J:253969 )

short vertebral column ( J:253969 )

abnormal chondrocyte morphology ( J:253969 )

• E15.5 chondrocytes have a swollen appearance, massive expansion of the endoplasmic rediculum, and disruption of the golgi apparatus

delayed bone mineralization ( J:253969 )

delayed bone ossification ( J:253969 )

• assessment of the humeri at E15.5 finds delayed formation of the primary ossificatiion center

limbs/digits/tail

short limbs ( J:253969 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
achondrogenesis type IA		DOID:0080054	OMIM:200600	J:253969

Genotype
MGI:3818063

cx55

• Allelic Composition: Scnm1^tm1.1Mm/Scnm1^tm1.1Mm; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * FVB * SJL

growth/size/body

decreased body weight ( J:141236 )

• mice weigh 50% of wild-type