Phenotypes associated with this allele

• Allele Symbol: Nfib^tm1Rmg
• Allele Name: targeted mutation 1, Richard M Gronostajski
• Allele ID: MGI:3530139
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nfib^tm1Rmg/Nfib^tm1Rmg	involves: 129P2/OlaHsd	MGI:5052294
hm2	Nfib^tm1Rmg/Nfib^tm1Rmg	involves: 129P2/OlaHsd * Black Swiss	MGI:3530491
hm3	Nfib^tm1Rmg/Nfib^tm1Rmg	involves: 129P2/OlaHsd * C57BL/6	MGI:3530497
hm4	Nfib^tm1Rmg/Nfib^tm1Rmg	involves: 129P2/OlaHsd * FVB/N	MGI:3530502
ht5	Nfib^tm1Rmg/Nfib^+	involves: 129P2/OlaHsd * Black Swiss	MGI:3530495
ht6	Nfib^tm1Rmg/Nfib^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3530500
ht7	Nfib^tm1Rmg/Nfib^+	involves: 129P2/OlaHsd * FVB/N	MGI:3530503

Genotype
MGI:5052294

hm1

• Allelic Composition: Nfib^tm1Rmg/Nfib^tm1Rmg
• Genetic Background: involves: 129P2/OlaHsd

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

respiratory system

abnormal lung development ( J:173651 )

• at E18.5, mice exhibit decreased differentiation of epithelial type I, type II, ciliated, and Clara cells compared to in wild-type mice

abnormal respiratory system physiology ( J:173651 )

• at E18.5, lung cells exhibit increased in epithelial (Ttf1+) and mesenchymal (Ttf1-) cell proliferation compared with cells mice

• however, apoptosis rates are normal

Genotype
MGI:3530491

hm2

• Allelic Composition: Nfib^tm1Rmg/Nfib^tm1Rmg
• Genetic Background: involves: 129P2/OlaHsd * Black Swiss

mortality/aging

neonatal lethality, complete penetrance ( J:96006 )

• no homozygotes survived for 24 hours after birth

respiratory system

abnormal lung morphology ( J:96006 )

• observed minor surface indentations in E15.5 lungs and deep clefts or ruffles at E18.5

• higher levels of proliferation in E18.5 lung as detected by a fourfold increase in PCNA transcripts and a substantial increase in the total DNA in the lung but no differences in lung size

abnormal lung development ( J:96006 )

• E17.5 lungs were severely defective in maturation and resembled the less-mature E15.5 wildtype lungs, however morphology at E15.5 was normal indicating that lung development is arrested between E15.5 and E16.5

absent lung saccules ( J:96006 )

• E17.5 lungs lacked saccules

nervous system

abnormal hippocampus development ( J:96006 )

• a reduction in the entire hippocampal primordium at E15.5 and displayed severe disruptions in the formation of the hippocampus, with the entire CA3 region absent or severely reduced at E17.5

absent cerebellar foliation ( J:96006 )

• cerebellum appears unfoliated at E18.5

enlarged brain ventricles ( J:96006 )

• enlarged ventricles

absent corpus callosum ( J:96006 )

• exhibit agenesis of the corpus callosum

• complete absence of GFAP labeling in the indusium griseum and the glial wedge and a reduction in the midline zipper glia, indicating a loss or reduction of glial populations in the midline

abnormal pons morphology ( J:96006 )

• the basilar pons was virtually absent in the hindbrain, with only a small cap of cells remaining at E16.5 to E18.5 and the rest of the hindbrain appeared normal

abnormal hippocampus CA3 region morphology ( J:96006 )

• the entire CA3 region absent or severely reduced at E17.5

absent hippocampus CA3 region ( J:96006 )

absent dentate gyrus ( J:96006 )

• at E17.5 the dentate gyrus was absent

abnormal hippocampal fimbria morphology ( J:96006 )

• reduced fimbria in E17.5 hippocampus

abnormal glial cell morphology ( J:96006 )

• complete absence of GFAP labeling in the indusium griseum and the glial wedge and a reduction in the midline zipper glia, indicating a loss or reduction of glial populations in midline

Genotype
MGI:3530497

hm3

• Allelic Composition: Nfib^tm1Rmg/Nfib^tm1Rmg
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

respiratory system

abnormal lung morphology ( J:96006 )

• observed minor surface indentations in E15.5 lungs and deep clefts or ruffles at E18.5

• higher levels of proliferation in E18.5 lung as detected by a fourfold increase in PCNA transcripts and a substantial increase in the total DNA in the lung but no differences in lung size

abnormal lung development ( J:96006 )

• E17.5 lungs were severely defective in maturation and resembled the less-mature E15.5 wildtype lungs however morphology at E15.5 was normal indicating that lung development is arrested between E15.5 and E16.5

absent lung saccules ( J:96006 )

• E17.5 lungs lacked saccules

nervous system

abnormal hippocampus development ( J:96006 )

• a reduction in the entire hippocampal primordium at E15.5 and displayed more severe disruptions in the formation of the hippocampus, with the entire CA3 region absent or severely reduced, than on a mixed Black Swiss/129P2 background

absent cerebellar foliation ( J:96006 )

• cerebellum appears unfoliated at E18.5

enlarged brain ventricles ( J:96006 )

• enlarged ventricles

absent corpus callosum ( J:96006 )

• exhibit agenesis of the corpus callosum

• complete absence of GFAP labeling in the indusium griseum and the glial wedge and a reduction in the midline zipper glia, indicating a loss or reduction of glial populations in these areas

abnormal pons morphology ( J:96006 )

• the basilar pons was virtually absent in the hindbrain, with only a small cap of cells remaining at E16.5 to E18.5 and the rest of the hindbrain appeared normal

abnormal hippocampus CA3 region morphology ( J:96006 )

• the entire CA3 region is absent or severely reduced

absent hippocampus CA3 region ( J:96006 )

absent dentate gyrus ( J:96006 )

• at E17.5 the dentate gyrus was absent

abnormal hippocampal fimbria morphology ( J:96006 )

• greatly reduced fimbria in E17.5 hippocampus

abnormal cerebellar granule cell morphology ( J:121963 )

• at E18, axon formation by cerebrellar granule neurons (GCNs) is altered

abnormal glial cell morphology ( J:96006 )

• complete absence of GFAP labeling in the indusium griseum and the glial wedge and a reduction in the midline zipper glia, indicating a loss or reduction of glial populations in the midline

craniofacial

abnormal craniofacial development ( J:177282 )

• fetuses exhibit delayed cranial bone growth but without evidence of premature suture fusion

growth/size/body

decreased fetal size ( J:177282 )

• fetuses exhibit reduced overall size

digestive/alimentary system

abnormal major salivary gland morphology ( J:218202 )

• at E18.5, mutant submandibular glands and sublingual glands are hard to distinguish unlike in wild-type controls

abnormal submandibular gland development ( J:218202 )

• at E18.5, mutant submandibular glands have completely branched and canaliculized ducts but show signs of underdeveloped lobules that lack tubule secretory cells and ducts are connected directly with terminal buds (i.e. poor lumen formation)

• at E18.5, mutant inner tubule cells fail to differentiate and the overall morphology of terminal buds is similar to that of wild-type controls at E16.5

• at E16.5, mutant inner duct tubule cells are polygonal in shape and disorganized whereas wild-type controls are cuboidal and aligned in a row

• at E18.5, mutant proacinar cells are located at the distal end of the bud and lack secretory granules

• at E18.5, mutant submandibular glands fail to show apical expression of the water channel aquaporin 5 and display absence of staining for SMGC (a marker for tubule secretory cells) throughout the gland

• at E18.5, mutant submandibular glands maintain apicobasal cell polarity but show altered ZO-1 organization and fail to form lumens in both acinar and ductal structures or, in some cases, show poorly formed lumens

• mucin presence and distribution is altered at E16.5 and E18.5; mucin is expressed only in E18.5 wild-type glands

decreased submandibular gland size ( J:218202 )

• at E18.5, mutant submandibular glands display a marked decrease in size (~1.5 mm in length and 1.3 mm in width) relative to wild-type glands (~2.5 mm in length and 1.5 mm in width)

submandibular gland hypoplasia ( J:218202 )

• at E18.5, mutant submandibular glands display poorly developed lobular regions and a small round structure, indicating hypoplasia

endocrine/exocrine glands

abnormal major salivary gland morphology ( J:218202 )

• at E18.5, mutant submandibular glands and sublingual glands are hard to distinguish unlike in wild-type controls

abnormal submandibular gland development ( J:218202 )

• at E18.5, mutant submandibular glands have completely branched and canaliculized ducts but show signs of underdeveloped lobules that lack tubule secretory cells and ducts are connected directly with terminal buds (i.e. poor lumen formation)

• at E18.5, mutant inner tubule cells fail to differentiate and the overall morphology of terminal buds is similar to that of wild-type controls at E16.5

• at E16.5, mutant inner duct tubule cells are polygonal in shape and disorganized whereas wild-type controls are cuboidal and aligned in a row

• at E18.5, mutant proacinar cells are located at the distal end of the bud and lack secretory granules

• at E18.5, mutant submandibular glands fail to show apical expression of the water channel aquaporin 5 and display absence of staining for SMGC (a marker for tubule secretory cells) throughout the gland

• at E18.5, mutant submandibular glands maintain apicobasal cell polarity but show altered ZO-1 organization and fail to form lumens in both acinar and ductal structures or, in some cases, show poorly formed lumens

• mucin presence and distribution is altered at E16.5 and E18.5; mucin is expressed only in E18.5 wild-type glands

decreased submandibular gland size ( J:218202 )

• at E18.5, mutant submandibular glands display a marked decrease in size (~1.5 mm in length and 1.3 mm in width) relative to wild-type glands (~2.5 mm in length and 1.5 mm in width)

submandibular gland hypoplasia ( J:218202 )

• at E18.5, mutant submandibular glands display poorly developed lobular regions and a small round structure, indicating hypoplasia

Genotype
MGI:3530502

hm4

• Allelic Composition: Nfib^tm1Rmg/Nfib^tm1Rmg
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

respiratory system

abnormal lung morphology ( J:96006 )

• observed minor surface indentations in E15.5 lungs and deep clefts or ruffles at E18.5

• higher levels of proliferation in E18.5 lung as detected by a fourfold increase in PCNA transcripts and a substantial increase in the total DNA in the lung but no differences in lung size

abnormal lung development ( J:96006 )

• E17.5 lungs were severely defective in maturation and resembled the less-mature E15.5 wildtype lungs however morphology at E15.5 was normal indicating that lung development is arrested between E15.5 and E16.5

absent lung saccules ( J:96006 )

• E17.5 lungs lacked saccules

Genotype
MGI:3530495

ht5

• Allelic Composition: Nfib^tm1Rmg/Nfib⁺
• Genetic Background: involves: 129P2/OlaHsd * Black Swiss

mortality/aging

neonatal lethality, incomplete penetrance ( J:96006 )

• ~60% survive 24 hours after birth

respiratory system

abnormal lung development ( J:96006 )

• E17.5 lungs had a developmental delay in maturation

small lung saccule ( J:96006 )

• E17.5 lungs had smaller saccules

nervous system

abnormal corpus callosum morphology ( J:96006 )

• displayed agenesis of the corpus callosum with the formation of Probst bundles at the midline

• although all three midline glial populations are present, the indusium griseum glia appeared disorganized

abnormal glial cell morphology ( J:96006 )

• although all three midline glial populations are present, the indusium griseum glia appeared disorganized

Genotype
MGI:3530500

ht6

• Allelic Composition: Nfib^tm1Rmg/Nfib⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

postnatal lethality, incomplete penetrance ( J:96006 )

• only about 55% survive to 14 days after birth

respiratory system

abnormal lung development ( J:96006 )

• E17.5 lungs had a developmental delay in maturation

small lung saccule ( J:96006 )

• E17.5 lungs had smaller saccules

nervous system

abnormal corpus callosum morphology ( J:96006 )

• displayed a less severe callosal phenotype with the formation of Probst bundles at the midline than heterozygotes on the mixed Black Swiss background

• reduction in all three midline glial populations of the corpus callosum

abnormal glial cell morphology ( J:96006 )

• reduction in all three midline glial populations of the corpus callosum

Genotype
MGI:3530503

ht7

• Allelic Composition: Nfib^tm1Rmg/Nfib⁺
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

mortality/aging ( J:96006 )

N • little or no loss of heterozygotes at 14 days after birth

respiratory system

abnormal lung development ( J:96006 )

• E17.5 lungs had a developmental delay in maturation

small lung saccule ( J:96006 )

• E17.5 lungs had smaller saccules