Phenotypes associated with this allele

• Allele Symbol: Fgf9^tm1Dor
• Allele Name: targeted mutation 1, David Ornitz
• Allele ID: MGI:2135961
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fgf9^tm1Dor/Fgf9^tm1Dor	involves: 129S6/SvEvTac	MGI:5538518
hm2	Fgf9^tm1Dor/Fgf9^tm1Dor	involves: 129S6/SvEvTac * C57BL/6	MGI:2172287
hm3	Fgf9^tm1Dor/Fgf9^tm1Dor	involves: C57BL/6J	MGI:3529279
ht4	Fgf9^tm1Dor/Fgf9^+	involves: 129S6/SvEvTac	MGI:3840444
ht5	Fgf9^Eks/Fgf9^tm1Dor	involves: 129S6/SvEvTac * C57BL/6J * DBA/2J	MGI:3840443
cx6	Fgf9^tm1Dor/Fgf9^+ Fgfr3^tm1.1Aomw/Fgfr3^+	involves: 129 * BALB/c * C57BL/6	MGI:3831412
cx7	Fgf8^tm1Mrc/Fgf8^+ Fgf9^tm1Dor/Fgf9^+ Fgfr3^tm1.1Aomw/Fgfr3^+	involves: 129 * BALB/c * C57BL/6	MGI:3831411
cx8	Fgf2^tm1Doe/Fgf2^tm1Doe Fgf9^tm1Dor/Fgf9^tm1Dor	involves: C57BL/6J	MGI:3529284

Genotype
MGI:5538518

hm1

• Allelic Composition: Fgf9^tm1Dor/Fgf9^tm1Dor
• Genetic Background: involves: 129S6/SvEvTac

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

respiratory system

abnormal lung-associated mesenchyme development ( J:107406 )

• E12.5 lungs lack sub-mesothelial mesenchyme to a greater extent than sub-epithelial mesenchyme resulting in an irregularly shaped distal mesenchymal edge

Genotype
MGI:2172287

hm2

• Allelic Composition: Fgf9^tm1Dor/Fgf9^tm1Dor
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

mortality/aging

perinatal lethality, complete penetrance ( J:68379 )

• homozygotes die at birth

neonatal lethality, complete penetrance ( J:69852 )

• mutants die shortly after birth

reproductive system

abnormal testis morphology ( J:68379 )

• all mutant testes have reduced mesenchyme relative to controls

• testis growth, cord formation, and Sertoli and Leydig cell differentiation are disrupted in most XY gonads by E13.5-E14.5

decreased number of peritubular myoid cells ( J:68379 )

• depletion of peritubular myoid cells in XY gonads

abnormal Sertoli cell development ( J:68379 )

• two E13.5 XY gonads show impaired Sertoli cell differentiation

abnormal testis cord formation ( J:68379 )

• disrupted testicular cord formation in XY gonads

disorganized testis cords ( J:68379 )

• testis from phenotypically male mice has disorganized testicular cords

abnormal Leydig cell differentiation ( J:68379 )

• Ledyig cell differentiation is disrupted in most XY gonads

testis hypoplasia ( J:68379 )

• some gonads had disorganized cord development and depleted germ cell populations; all had reduced amounts of mesenchyme

• at E18.5, 2 of 24 homozygotes examined were identified as phenotypic males and showed testicular hypoplasia

epididymis hypoplasia ( J:68379 )

• phenotypically male embryos exhibit epididymal hypoplasia

abnormal primary sex determination ( J:68379 )

ovotestis ( J:68379 )

• at E18.5, one XY gonad displayed both epididymal-like and uterine tissue

• at E18.5, all 15 gonads from phenotypically female XY mice exhibited predominantly ovarian histology; however, 2 displayed occasional testis cord structures

primary sex reversal ( J:68379 )

• at E18.5, 22 of 24 homozygotes examined had grossly female internal reproductive organs, suggesting male to female sex reversal

• 10 of 14 phenotypic females were in fact genotypic males (XY)

respiratory system

abnormal mesenchymal cell proliferation involved in lung development ( J:69852 )

• lungs exhibit overall reduced mesenchyme and reduced mesenchymal proliferation at E10.5-E11.5, however no differences in proliferation are seen at E13.5

abnormal branching involved in lung morphogenesis ( J:69852 )

• lungs display decreased branching of airways as exhibited by the absence of secondary branching of the accessory lobe at E13.5, dilated and unbranched peripheral buds at E12.5-E13.5, fewer small diameter airways at E13.5-E18.5, and fewer alveolar sacs than controls

• however, mutants do show significant distal airspace formation and pneumocyte differentiation

decreased lung weight ( J:69852 )

• mean weight of E18.5 lungs is 29% that of controls

pulmonary hypoplasia ( J:69852 )

• 100% penetrance of lung hypoplasia

respiratory failure ( J:69852 )

• by 30 minutes after Caesarian section, mutants exhibit agonal breathing and cyanosis

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:68379 )

N • mutants exhibit normal pituitary development

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

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

abnormal testis morphology ( J:68379 )

• all mutant testes have reduced mesenchyme relative to controls

• testis growth, cord formation, and Sertoli and Leydig cell differentiation are disrupted in most XY gonads by E13.5-E14.5

decreased number of peritubular myoid cells ( J:68379 )

• depletion of peritubular myoid cells in XY gonads

abnormal Sertoli cell development ( J:68379 )

• two E13.5 XY gonads show impaired Sertoli cell differentiation

abnormal testis cord formation ( J:68379 )

• disrupted testicular cord formation in XY gonads

disorganized testis cords ( J:68379 )

• testis from phenotypically male mice has disorganized testicular cords

abnormal Leydig cell differentiation ( J:68379 )

• Ledyig cell differentiation is disrupted in most XY gonads

testis hypoplasia ( J:68379 )

• some gonads had disorganized cord development and depleted germ cell populations; all had reduced amounts of mesenchyme

• at E18.5, 2 of 24 homozygotes examined were identified as phenotypic males and showed testicular hypoplasia

craniofacial

cleft palate ( J:69852 )

• about 40% of homozygous embryos exhibit cleft palate

digestive/alimentary system

cleft palate ( J:69852 )

• about 40% of homozygous embryos exhibit cleft palate

abnormal cecum morphology ( J:104353 )

• absent cecal development, lacking both mesenchymal expansion and an epithelial bud

• cell proliferation in the embryonic cecum is reduced by 40% in epithelium and 47% in mesenchyme

• mesenchymal proliferation in cecal buds is significantly less than mesenchymal proliferation in the adjacent small intestine or colon, opposite of what is seen in wild-type

abnormal small intestine morphology ( J:139005 )

• there is a 35% reduction in the length of the small intestine at E18.5 compared to controls

• differences in length are first evident at E14.5

• lumen diameter is unaffected in these mice suggesting the length of the intestine is altered in one dimension

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

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

abnormal digestive system physiology ( J:139005 )

• proliferation of fibroblasts found in the proximal and distal small intestine mesenchyme is significantly reduced between E14.5 and E18.5

cardiovascular system

dilated heart atrium ( J:69852 )

• variable dilation of cardiac atria is observed at E14.5-E18.5

dilated heart ventricle ( J:69852 )

• variable dilation of cardiac ventricles is observed at E14.5-E18.5

growth/size/body

cleft palate ( J:69852 )

• about 40% of homozygous embryos exhibit cleft palate

decreased fetal weight ( J:69852 )

• total mean body weight at E18.5 is 84% of controls

homeostasis/metabolism

cyanosis ( J:69852 )

• E18.5 pups can breathe initially, however they become severely cyanotic shortly thereafter

hypoxia ( J:69852 )

cellular

abnormal mesenchymal cell proliferation involved in lung development ( J:69852 )

• lungs exhibit overall reduced mesenchyme and reduced mesenchymal proliferation at E10.5-E11.5, however no differences in proliferation are seen at E13.5

Genotype
MGI:3529279

hm3

• Allelic Composition: Fgf9^tm1Dor/Fgf9^tm1Dor
• Genetic Background: involves: C57BL/6J

cardiovascular system

abnormal heart development ( J:95803 )

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

increased heart atrium size ( J:95803 )

• at E12.5 the atria are enlarged

heart hypoplasia ( J:95803 )

• at E12.5 the hearts are smaller with a disproportionate loss of tissue at the apex of the heart and in the regions around the interventricular groove, however at E18.5 the patterning of the ventricles, septum, valves, and outflow tract are normal

dilated heart left ventricle ( J:95803 )

• biventricular dilation is seen in newborn mutants

dilated heart right ventricle ( J:95803 )

• biventricular dilation is seen in newborn mutants

abnormal fetal cardiomyocyte proliferation ( J:95803 )

• decreased myocardial proliferation is seen at the apex of the heart and in the regions around the interventricular groove, however no significant difference in the levels of apoptosis is seen

muscle

abnormal fetal cardiomyocyte proliferation ( J:95803 )

• decreased myocardial proliferation is seen at the apex of the heart and in the regions around the interventricular groove, however no significant difference in the levels of apoptosis is seen

cellular

abnormal fetal cardiomyocyte proliferation ( J:95803 )

• decreased myocardial proliferation is seen at the apex of the heart and in the regions around the interventricular groove, however no significant difference in the levels of apoptosis is seen

Genotype
MGI:3840444

ht4

• Allelic Composition: Fgf9^tm1Dor/Fgf9⁺
• Genetic Background: involves: 129S6/SvEvTac

skeleton

synostosis ( J:146802 )

• in the cartilaginous and skeletal components of the elbow joint

Genotype
MGI:3840443

ht5

• Allelic Composition: Fgf9^Eks/Fgf9^tm1Dor
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * DBA/2J

skeleton

synostosis ( J:146802 )

• in the cartilaginous and skeletal components of the elbow joint

Genotype
MGI:3831412

cx6

• Allelic Composition: Fgf9^tm1Dor/Fgf9⁺; Fgfr3^tm1.1Aomw/Fgfr3⁺
• Genetic Background: involves: 129 * BALB/c * C57BL/6

hearing/vestibular/ear

increased or absent threshold for auditory brainstem response ( J:143356 )

• increased ABR threshold at all test frequencies

impaired hearing ( J:143356 )

Genotype
MGI:3831411

cx7

• Allelic Composition: Fgf8^tm1Mrc/Fgf8⁺; Fgf9^tm1Dor/Fgf9⁺; Fgfr3^tm1.1Aomw/Fgfr3⁺
• Genetic Background: involves: 129 * BALB/c * C57BL/6

hearing/vestibular/ear

increased or absent threshold for auditory brainstem response ( J:143356 )

• increased ABR threshold at all test frequencies

impaired hearing ( J:143356 )

Genotype
MGI:3529284

cx8

• Allelic Composition: Fgf2^tm1Doe/Fgf2^tm1Doe; Fgf9^tm1Dor/Fgf9^tm1Dor
• Genetic Background: involves: C57BL/6J

cardiovascular system

increased heart atrium size ( J:95803 )

• at E12.5 the atria are enlarged

heart hypoplasia ( J:95803 )

• at E12.5, the hearts are smaller with a disproportionate loss of tissue at the apex of the heart and in the regions around the interventricular groove; however, the patterning of the ventricles, septum, valves, and outflow tract are normal

• double homozygotes are indistinguishable from Fgf9 single homozygotes