Phenotypes associated with this allele

• Allele Symbol: Folr1^tm1Fnn
• Allele Name: targeted mutation 1, Richard H Finnell
• Allele ID: MGI:2383986
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Folr1^tm1Fnn/Folr1^tm1Fnn	involves: 129 * C57BL/6J	MGI:3575524
hm2	Folr1^tm1Fnn/Folr1^tm1Fnn	involves: 129P2/OlaHsd * C57BL/6J	MGI:3615352
ht3	Folr1^tm1Fnn/Folr1^+	involves: 129 * C57BL/6J	MGI:3575525
ht4	Folr1^tm1Fnn/Folr1^+	involves: 129P2/OlaHsd * C57BL/6J	MGI:3615351

Genotype
MGI:3575524

hm1

• Allelic Composition: Folr1^tm1Fnn/Folr1^tm1Fnn
• Genetic Background: involves: 129 * C57BL/6J

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

homeostasis/metabolism

abnormal folic acid level ( J:96380 )

• the level of folate in the plasma and colonic mucosa is decreased compared to wild-type and heterozygous littermates

Genotype
MGI:3615352

hm2

• Allelic Composition: Folr1^tm1Fnn/Folr1^tm1Fnn
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:57765 )

• in the absence of supplemental folic acid, all homozygous mutant embryos develop abnormally and die by E10

• folate supplemention of pregnant heterozygous dams restores viability and reverses the neural tube defect in 12 of 13 nullizygous pups

embryo

abnormal neural crest cell migration ( J:57765 )

• at E8.5, homozygotes exhibit abnormal migration of the neural crest cells, as only small aggregates of cells are identified in the mesenchyme in the region of the first branchial arch

absent first pharyngeal arch ( J:57765 )

• at E8.5, homozygotes display absence of the first branchial arch

incomplete embryo turning ( J:57765 )

• at E8.5, homozygous mutant embryos fail to initiate axial turning and remain in the characteristic S-shape as opposed to a more advanced C-shape

embryonic growth retardation ( J:57765 )

• at E8.5, E9.5 and E10.5, homozygotes exhibit a significant delay in embryonic growth and development relative to wild-type embryos

abnormal embryonic neuroepithelial layer differentiation ( J:57765 )

• the mutant neuroepithelium appears widely flared and thinned at the level of the otic placode; caudal to the otic pit, the neuroepithelium remains open

decreased embryonic neuroepithelium thickness ( J:57765 )

• at E8.5, homozygotes exhibit a thin neuroepithelium (only 1 or 2 cells in thickness) at the level of forebrain and midbrain

delayed rostral neuropore closure ( J:57765 )

• at E8.5, homozygotes exhibit delayed development of the anterior neural folds; as a result, they fail to complete neural closure by E9.5

incomplete rostral neuropore closure ( J:57765 )

• homozygotes fail to complete neural closure by E9.5

incomplete somite formation ( J:57765 )

• at E8.5 and E9.5, homozygous mutant embryos have significantly fewer somites than age-matched wild-type or heterozygous embryos

growth/size/body

embryonic growth retardation ( J:57765 )

• at E8.5, E9.5 and E10.5, homozygotes exhibit a significant delay in embryonic growth and development relative to wild-type embryos

nervous system

abnormal embryonic neuroepithelial layer differentiation ( J:57765 )

• the mutant neuroepithelium appears widely flared and thinned at the level of the otic placode; caudal to the otic pit, the neuroepithelium remains open

decreased embryonic neuroepithelium thickness ( J:57765 )

• at E8.5, homozygotes exhibit a thin neuroepithelium (only 1 or 2 cells in thickness) at the level of forebrain and midbrain

delayed rostral neuropore closure ( J:57765 )

• at E8.5, homozygotes exhibit delayed development of the anterior neural folds; as a result, they fail to complete neural closure by E9.5

incomplete rostral neuropore closure ( J:57765 )

• homozygotes fail to complete neural closure by E9.5

absent forebrain ( J:57765 )

• at E8.5, homozygotes show absence of forebrain formation in the cephalic neural tube

absent trigeminal ganglion ( J:57765 )

• at E8.5, homozygotes display absence of the trigeminal ganglia

craniofacial

abnormal otic pit morphology ( J:57765 )

• at E8.5, homozygotes display a thin neuroepithelium and a poorly developed otic pit at the level of the otic placode

absent first pharyngeal arch ( J:57765 )

• at E8.5, homozygotes display absence of the first branchial arch

vision/eye

absent optic vesicle ( J:57765 )

• at E8.5, homozygotes show absence of optic vesicle formation in the cephalic neural tube

hearing/vestibular/ear

abnormal otic pit morphology ( J:57765 )

• at E8.5, homozygotes display a thin neuroepithelium and a poorly developed otic pit at the level of the otic placode

cellular

abnormal neural crest cell migration ( J:57765 )

• at E8.5, homozygotes exhibit abnormal migration of the neural crest cells, as only small aggregates of cells are identified in the mesenchyme in the region of the first branchial arch

Genotype
MGI:3575525

ht3

• Allelic Composition: Folr1^tm1Fnn/Folr1⁺
• Genetic Background: involves: 129 * C57BL/6J

neoplasm

increased incidence of tumors by chemical induction ( J:96380 )

• 38 weeks after treatment with azoxymethane, about 4-fold more focal inflammatory lesions are seen and 5 out of 10 treated heterozygotes developed adenocarcinomas compared to 3 out of 11 wild-type mice

digestive/alimentary system

abnormal crypts of Lieberkuhn morphology ( J:96380 )

• the number of colonic cells per crypt column is increased

homeostasis/metabolism

abnormal folic acid level ( J:96380 )

• the level of folate in the plasma and colonic mucosa is decreased compared to wild-type littermates

increased physiological sensitivity to xenobiotic ( J:96380 )

• 38 weeks after treatment with azoxymethane, about 4-fold more focal inflammatory lesions are seen

increased incidence of tumors by chemical induction ( J:96380 )

• 38 weeks after treatment with azoxymethane, about 4-fold more focal inflammatory lesions are seen and 5 out of 10 treated heterozygotes developed adenocarcinomas compared to 3 out of 11 wild-type mice

endocrine/exocrine glands

abnormal crypts of Lieberkuhn morphology ( J:96380 )

• the number of colonic cells per crypt column is increased

Genotype
MGI:3615351

ht4

• Allelic Composition: Folr1^tm1Fnn/Folr1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

homeostasis/metabolism

increased circulating homocysteine level ( J:57765 )

• on a reduced folic acid diet, non-pregnant heterozygous dams show significantly increased plasma homocysteine concentrations (30 M) relative to wild-type dams (7.5 M)

• however, on a normal folate rodent diet, heterozygous dams exhibit normal plasma homocysteine concentrations relative to wild-type dams (average 1.4-6 M)