Phenotypes associated with this allele

• Allele Symbol: Atf4^tm1Tow
• Allele Name: targeted mutation 1, Timothy Townes
• Allele ID: MGI:2180373
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Atf4^tm1Tow/Atf4^tm1Tow	either: (involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J * NIH Black Swiss) or (involves: 129P2/OlaHsd * C57BL/6J * NIH Black Swiss)	MGI:4360506
hm2	Atf4^tm1Tow/Atf4^tm1Tow	either: (involves: 129P2/OlaHsd * NIH Black Swiss) or (involves: 129S1/Sv * 129X1/SvJ * NIH Black Swiss)	MGI:3777112
hm3	Atf4^tm1Tow/Atf4^tm1Tow	involves: 129S1/Sv * 129X1/SvJ * NIH Black Swiss	MGI:3043294
cx4	Atf4^tm1Tow/Atf4^+ Ptprv^tm1Asmi/Ptprv^+	either: (involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J * NIH Black Swiss) or (involves: 129P2/OlaHsd * C57BL/6J * NIH Black Swiss)	MGI:4360508
cx5	Atf4^tm1Tow/Atf4^+ Satb2^tm1Rug/Satb2^+	either: (involves: 129P2/OlaHsd * NIH Black Swiss) or (involves: 129S1/Sv * 129X1/SvJ * NIH Black Swiss)	MGI:3696661
cx6	Atf4^tm1Tow/Atf4^tm1Tow Hivep3^tm1Glm/Hivep3^tm1Glm	involves: 129 * C57BL/6	MGI:5550513

Genotype
MGI:4360506

hm1

• Allelic Composition: Atf4^tm1Tow/Atf4^tm1Tow
• Genetic Background: either: (involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J * NIH Black Swiss) or (involves: 129P2/OlaHsd * C57BL/6J * NIH Black Swiss)

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

Smaller fat pads in Atf4^tm1Tow/Atf4^tm1Tow mice

homeostasis/metabolism

increased insulin secretion ( J:152695 )

decreased circulating glucose level ( J:152695 )

• at 2 weeks, 1 month, and 2 months

increased circulating insulin level ( J:152695 )

impaired gluconeogenesis ( J:152695 )

• reduced after pyruvate challenge

improved glucose tolerance ( J:152695 )

increased insulin sensitivity ( J:152695 )

• in mice and liver, muscle, and fat cells but not hepatocytes

endocrine/exocrine glands

increased pancreatic beta cell proliferation ( J:152695 )

• beta cell proliferation is increased compared to in wild-type mice

increased pancreatic beta cell mass ( J:152695 )

• beta cell area and mass are increased compared to in wild-type mice

increased insulin secretion ( J:152695 )

adipose tissue

decreased total fat pad weight ( J:152695 )

• at 8 weeks, mice exhibit decreased fad pad size and weight compared to in wild-type mice

cellular

increased pancreatic beta cell proliferation ( J:152695 )

• beta cell proliferation is increased compared to in wild-type mice

Genotype
MGI:3777112

hm2

• Allelic Composition: Atf4^tm1Tow/Atf4^tm1Tow
• Genetic Background: either: (involves: 129P2/OlaHsd * NIH Black Swiss) or (involves: 129S1/Sv * 129X1/SvJ * NIH Black Swiss)

Atf4^tm1Tow/Atf4^tm1Tow mice show pancreatic hypotrophy

cellular

abnormal osteoblast differentiation ( J:129974 )

• delay in differentiation

craniofacial

abnormal neurocranium morphology ( J:89403 )

• skull trabeculae were short and thin, putatively compromising the protection of the brain during delivery

large fontanelles ( J:89403 )

• widened at birth

abnormal frontal bone morphology ( J:89403 )

• decreased mineralization

abnormal parietal bone morphology ( J:89403 )

• decreased mineralization

digestive/alimentary system

abnormal pancreatic acinus morphology ( J:129974 )

• number of acini is greatly reduced

• pancreatic acini are dispersed and are not in close proximity to neighboring acini resulting in an expanded extracellular space

• the centroacinar duct is greatly expanded in adults

abnormal pancreatic acinar cell morphology ( J:129974 )

• acinar cell size is greatly reduced

abnormal pancreatic acinar cell zymogen granule morphology ( J:129974 )

• acinar cells appear smaller with less zymogen granule content

exocrine pancreas hypoplasia ( J:89403 )

• exocrine pancreas of P4 mutants is severely underdeveloped

endocrine/exocrine glands

abnormal pancreas morphology ( J:129974 )

• adult pancreas contains numerous adipoctyes

abnormal pancreatic acinus morphology ( J:129974 )

• number of acini is greatly reduced

• pancreatic acini are dispersed and are not in close proximity to neighboring acini resulting in an expanded extracellular space

• the centroacinar duct is greatly expanded in adults

abnormal pancreatic acinar cell morphology ( J:129974 )

• acinar cell size is greatly reduced

abnormal pancreatic acinar cell zymogen granule morphology ( J:129974 )

• acinar cells appear smaller with less zymogen granule content

exocrine pancreas hypoplasia ( J:89403 )

• exocrine pancreas of P4 mutants is severely underdeveloped

skeleton

abnormal osteoblast differentiation ( J:129974 )

• delay in differentiation

abnormal neurocranium morphology ( J:89403 )

• skull trabeculae were short and thin, putatively compromising the protection of the brain during delivery

large fontanelles ( J:89403 )

• widened at birth

abnormal frontal bone morphology ( J:89403 )

• decreased mineralization

abnormal parietal bone morphology ( J:89403 )

• decreased mineralization

abnormal clavicle morphology ( J:89403 )

• decreased mineralization

decreased bone mineral density ( J:89403 )

abnormal bone trabecula morphology ( J:89403 )

• abnormal trabeculae

abnormal bone ossification ( J:89403 )

• normal skeletogenesis prior to E13, however defects were observed between E14 and E16

abnormal bone mineralization ( J:89403 )

• observed in both frontal and parietal bones, clavicles, and long bones

growth/size/body

abnormal frontal bone morphology ( J:89403 )

• decreased mineralization

Genotype
MGI:3043294

hm3

• Allelic Composition: Atf4^tm1Tow/Atf4^tm1Tow
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * NIH Black Swiss

mortality/aging

perinatal lethality, incomplete penetrance ( J:74479 )

• most mice died within an hour of birth, although some mice persisted

postnatal lethality, incomplete penetrance ( J:74479 )

• some mice that survived the perinatal period died within the first 3 weeks of life

cellular

decreased cell proliferation ( J:74479 )

growth/size/body

decreased body weight ( J:74479 )

decreased body length ( J:74479 )

postnatal growth retardation ( J:74479 )

hematopoietic system

absent common myeloid progenitor cells ( J:74479 )

• due to a cell-autonomous proliferation defect

anemia ( J:74479 )

• severe fetal anemia

• mice that survived the perinatal period had mild anemia

impaired hematopoiesis ( J:74479 )

• impaired fetal liver definitive hematopoiesis

decreased hematocrit ( J:74479 )

liver/biliary system

decreased hepatocyte number ( J:74479 )

• fetal liver hypoplasia

pale liver ( J:74479 )

• the fetal liver was pale

reproductive system

female infertility ( J:74479 )

♀ • inspite of having grossly normal ovaries

male infertility ( J:74479 )

♂ • most males that survived the perinatal period were infertile

reduced male fertility ( J:74479 )

♂ • mice that surivived the perinatal period and that were not completely sterile jad a reduced period of fertility and impregnated females at a reduced rate

vision/eye

microphthalmia ( J:74479 )

• severe microphthalmia with no recognizable lens, anterior chamber, iris, or vitreous body

• eye development was impaired after E14.5, when the lens normally undergoes rapid cellular proliferation

integument

delayed hair appearance ( J:74479 )

• by 1 week of age, surviving mice had only a sparse coat

• the delay resolved itself by adulthood

ruffled hair ( J:74479 )

Genotype
MGI:4360508

cx4

• Allelic Composition: Atf4^tm1Tow/Atf4⁺; Ptprv^tm1Asmi/Ptprv⁺
• Genetic Background: either: (involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J * NIH Black Swiss) or (involves: 129P2/OlaHsd * C57BL/6J * NIH Black Swiss)

homeostasis/metabolism

decreased circulating glucose level ( J:152695 )

increased circulating insulin level ( J:152695 )

endocrine/exocrine glands

increased pancreatic beta cell proliferation ( J:152695 )

• beta cell proliferation is increased compared to in wild-type mice

cellular

increased pancreatic beta cell proliferation ( J:152695 )

• beta cell proliferation is increased compared to in wild-type mice

Genotype
MGI:3696661

cx5

• Allelic Composition: Atf4^tm1Tow/Atf4⁺; Satb2^tm1Rug/Satb2⁺
• Genetic Background: either: (involves: 129P2/OlaHsd * NIH Black Swiss) or (involves: 129S1/Sv * 129X1/SvJ * NIH Black Swiss)

skeleton

abnormal bone structure ( J:115876 )

decreased bone volume ( J:115876 )

• bone volume/total volume is reduced from 15.5% in wild-type to 8.53% in mutants

decreased bone trabecula number ( J:115876 )

• trabecular numbers/mm are reduced from 4.54 in wild-type to 2.48 in mutants

decreased bone ossification ( J:115876 )

• display a marked reduction of bone formation at E15.5

Genotype
MGI:5550513

cx6

• Allelic Composition: Atf4^tm1Tow/Atf4^tm1Tow; Hivep3^tm1Glm/Hivep3^tm1Glm
• Genetic Background: involves: 129 * C57BL/6

Bone volume and trabeculae analysis in Hivep3^tm1GlmHivep3^tm1Glm and Atf4^tm1Tow/Atf4^tm1Tow Hivep3^tm1Glm/Hivep3^tm1Glm mice

skeleton

increased bone volume ( J:201597 )

increased trabecular bone thickness ( J:201597 )

increased bone ossification ( J:201597 )

• increased bone formation rate