Phenotypes associated with this allele

• Allele Symbol: Tgfa^tm1Unc
• Allele Name: targeted mutation 1, University of North Carolina
• Allele ID: MGI:1933208
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tgfa^tm1Unc/Tgfa^tm1Unc	involves: 129P2/OlaHsd * C57BL/6J	MGI:2174769
cx2	Egfr^Wa5/Egfr^+ Tgfa^tm1Unc/Tgfa^tm1Unc	involves: 129P2/OlaHsd * BALB/cAnN * C3H/HeN * C57BL/6J	MGI:3623314
cx3	Areg^tm1Dle/Areg^tm1Dle Egf^tm1Dle/Egf^tm1Dle Tgfa^tm1Unc/Tgfa^tm1Unc	involves: 129P2/OlaHsd * C57BL/6	MGI:2176534
cx4	Egf^tm1Dle/Egf^tm1Dle Ereg^tm1Dwt/Ereg^tm1Dwt Tgfa^tm1Unc/Tgfa^tm1Unc	involves: 129S6/SvEvTac * C57BL/6J	MGI:3512137

Genotype
MGI:2174769

hm1

• Allelic Composition: Tgfa^tm1Unc/Tgfa^tm1Unc
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

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

adipose tissue

abnormal adipose tissue distribution ( J:4605 )

• the dermal adipose layer is thinner compared to sex and weight matched normal littermates

craniofacial

orbicularis oculi muscle hypoplasia ( J:4605 )

• in some homozygotes hypoplasia of the orbicularis muscle is seen

growth/size/body

orbicularis oculi muscle hypoplasia ( J:4605 )

• in some homozygotes hypoplasia of the orbicularis muscle is seen

endocrine/exocrine glands

Meibomian gland hypoplasia ( J:4605 )

• in some homozygotes hypoplasia of the Meibomian gland is seen

vision/eye

abnormal eye morphology ( J:4605 )

• at 3 - 6 months of age, 40% of homozygotes display some eye abnormalities

retina neovascularization ( J:4605 )

abnormal anterior eye segment morphology ( J:4605 )

• anterior segment dysgenesis is seen as corneal fibrosis and vascularization, absence of Descemet's membrane and the anterior chamber, and incomplete iris differentiation

abnormal iris morphology ( J:4605 )

• incomplete iris differentiation

absent Descemet membrane ( J:4605 )

cornea scarring ( J:4605 )

absent eye anterior chamber ( J:4605 )

• absence of anterior chamber

ruptured lens capsule ( J:4605 )

• lens rupture is seen in some homozygotes

cataract ( J:4605 )

• seen in some homozygotes

microphthalmia ( J:4605 )

abnormal eyelid morphology ( J:4605 )

• mice with eyelid dysgenesis also display eyelid epithelial hyperplasia, accumulation of cellular debris and secretions, and ulceration and inflammation of the cornea

orbicularis oculi muscle hypoplasia ( J:4605 )

• in some homozygotes hypoplasia of the orbicularis muscle is seen

Meibomian gland hypoplasia ( J:4605 )

• in some homozygotes hypoplasia of the Meibomian gland is seen

abnormal eyelid development ( J:4605 )

• eyelid dysgenesis is sometimes observed

abnormal eyelid aperture ( J:4605 )

• partially or completely shut eyes

eyelid hyperplasia ( J:4605 )

• eyelid epithelial hyperplasia in mice with eyelid dysgenesis

eyelids open at birth ( J:4605 )

• partial opening of one or both eyes is seen in some homozygotes at birth and the exposed eyes often become bloody or purulent before scab formation

immune system

immune system phenotype ( J:4605 )

N • wound healing is similar to wild-type

cardiovascular system

cardiovascular system phenotype ( J:60750 )

N • cardiac valve size is similar to wild-type

retina neovascularization ( J:4605 )

muscle

orbicularis oculi muscle hypoplasia ( J:4605 )

• in some homozygotes hypoplasia of the orbicularis muscle is seen

integument

Meibomian gland hypoplasia ( J:4605 )

• in some homozygotes hypoplasia of the Meibomian gland is seen

disheveled coat ( J:4605 )

waved hair ( J:4605 )

• between 2 - 4 weeks of age the coat develops a wavy appearance

abnormal hair shaft morphology ( J:4605 )

• hair shafts have additional bends that do not coincide with the normal constrictions; however cuticle and root structure appear normal

abnormal hair medulla ( J:4605 )

• in some hair shafts irregular septulation of the medulla is seen

abnormal hair follicle morphology ( J:4605 )

• follicle bulbs extend deeper into the dermal adipose layer

abnormal hair follicle orientation ( J:4605 )

• at 10 days of age, hair follicles appear crowded, misaligned, and variably angled

• hair follicles with fully formed hairs are often seen growing horizontally along the subcutaneous muscle rather than toward the epidermis

curly vibrissae ( J:4605 )

• prior to the emergence of the coat, whiskers appear curly, kinked, or both

kinked vibrissae ( J:4605 )

• prior to the emergence of the coat, whiskers appear curly, kinked, or both

Genotype
MGI:3623314

cx2

• Allelic Composition: Egfr^Wa5/Egfr⁺; Tgfa^tm1Unc/Tgfa^tm1Unc
• Genetic Background: involves: 129P2/OlaHsd * BALB/cAnN * C3H/HeN * C57BL/6J

Phenotypes of Egfr^wa2/Egfr^Wa5 and Tgfa^tm1Unc/Tgfa^tm1Unc Egfr^Wa5/⁺ mice

growth/size/body

postnatal growth retardation ( J:92308 )

• reduced postnatal growth although size at birth is normal

• noticeably reduced in size by 1 week of age

• 25% reduction in body size in mice surviving to 6 weeks of age

craniofacial

small mandible ( J:92308 )

• smaller lower jaw

skeleton

small mandible ( J:92308 )

• smaller lower jaw

Genotype
MGI:2176534

cx3

• Allelic Composition: Areg^tm1Dle/Areg^tm1Dle; Egf^tm1Dle/Egf^tm1Dle; Tgfa^tm1Unc/Tgfa^tm1Unc
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

digestive/alimentary system

abnormal intestinal goblet cell morphology ( J:70183 )

• most homozygous villous goblet cells stained less robustly with mucicarmine, suggesting they are producing lower amounts of mucin

• the number of villous goblet cells was decreased 32% relative to wild-type villi

• not observed in mice homozygous for any pair-wise combination of these three genes

• reduced levels of trefoil production, a peptide family critical for mucosal defense and ulcer healing

abnormal small intestine morphology ( J:70183 )

• the weight/length ratio of the small intestine was reduced 37% in triple null pups; functional maturation at weaning age was not affected

abnormal small intestine crypts of Lieberkuhn morphology ( J:70183 )

• fewer crypt cells were proliferating in homozygous ileum compared to wild-type

duodenal lesions ( J:70183 )

• spontaneous lesions affecting mucosal integrity observed in 50% of samples; lesions varied from mild erosions to occasional perforations; not observed in mice homozygous for any pair-wise combination of these three genes

• more susceptible to induced duodenal lesions; cysteamine treatment produced more severe lesions than in wild-type mice

abnormal ileum morphology ( J:70183 )

• stunted villi with jagged or sheared tips; the average villus height in mutant ileum was reduced 47% relative to wild-type at three weeks, but only 11% at 5 weeks

• the muscularis mucosa layer was reduced in thickness at three weeks of age

endocrine/exocrine glands

abnormal small intestine crypts of Lieberkuhn morphology ( J:70183 )

• fewer crypt cells were proliferating in homozygous ileum compared to wild-type

abnormal branching of the mammary ductal tree ( J:54980 )

♀ • ducts in virgin pubescent glands hardly extended beyond the rudimentary anlage and only a few terminal end buds were observed at 6 weeks

♀ • at 12 weeks, ductal trees were underdeveloped and had persistent terminal end buds

abnormal mammary gland growth during pregnancy ( J:54980 )

♀ • during pregnancy, mammary glands exhibited defects in lobuloalveolar development; alveoli appear small and dense instead of engorged with fat droplets at day 18 of pregnancy

♀ • on day 2 of lactation, alveoli are compressed and overcrowded, and exhibit increased epithelial density with irregular, compact alveolar morphology observed

hypolactation ( J:54980 )

♀ • mutant mammary glands could not sustain lactation and expression of milk protein genes was decreased

♀ • pups did not thrive due to decreased milk production of dams

♀ • lactation improved with aged mothers

growth/size/body

decreased body weight ( J:70183 )

• a 40% reduction in the body weight of pups by 3 weeks was observed; partially attenuated by cross-fostering to wild-type dams

• by 7 weeks, weights were 15% reduced relative to wild-type, suggesting that a maternal lactation defect was partially responsible for the weight loss and this is overcome on a chow diet

weight loss ( J:54980 )

• accelerated with aging

postnatal growth retardation ( J:54980 )

• postnatal growth retardation of triple null pups was observed independent of maternal genotype

• more severe growth defects were seen when the mother was also triple null, and less severe growth defects were seen when the mother was wild-type

• control pups born to triple null mothers also exhibited growth retardation probably due to decreased milk production

reproductive system

abnormal mammary gland growth during pregnancy ( J:54980 )

♀ • during pregnancy, mammary glands exhibited defects in lobuloalveolar development; alveoli appear small and dense instead of engorged with fat droplets at day 18 of pregnancy

♀ • on day 2 of lactation, alveoli are compressed and overcrowded, and exhibit increased epithelial density with irregular, compact alveolar morphology observed

vision/eye

cornea opacity ( J:54980 )

• incidence noted as more frequent (80-90%) than the single Tgfa^tm1Unc homozygous mutants (40-50%)

microphthalmia ( J:54980 )

• incidence noted as more frequent (80-90%) than the single Tgfa^tm1Unc homozygous mutants (40-50%)

eyelids open at birth ( J:54980 )

• incidence noted as more frequent (80-90%) than the single Tgfa^tm1Unc homozygous mutants (40-50%)

immune system

dermatitis ( J:54980 )

• accelerated with aging

integument

abnormal branching of the mammary ductal tree ( J:54980 )

♀ • ducts in virgin pubescent glands hardly extended beyond the rudimentary anlage and only a few terminal end buds were observed at 6 weeks

♀ • at 12 weeks, ductal trees were underdeveloped and had persistent terminal end buds

abnormal mammary gland growth during pregnancy ( J:54980 )

♀ • during pregnancy, mammary glands exhibited defects in lobuloalveolar development; alveoli appear small and dense instead of engorged with fat droplets at day 18 of pregnancy

♀ • on day 2 of lactation, alveoli are compressed and overcrowded, and exhibit increased epithelial density with irregular, compact alveolar morphology observed

hypolactation ( J:54980 )

♀ • mutant mammary glands could not sustain lactation and expression of milk protein genes was decreased

♀ • pups did not thrive due to decreased milk production of dams

♀ • lactation improved with aged mothers

dermatitis ( J:54980 )

• accelerated with aging

alopecia ( J:54980 )

• accelerated with aging

waved hair ( J:54980 )

• accelerated with aging

curly vibrissae ( J:54980 )

spontaneous skin ulceration ( J:54980 )

• accelerated with aging

cellular

abnormal intestinal goblet cell morphology ( J:70183 )

• most homozygous villous goblet cells stained less robustly with mucicarmine, suggesting they are producing lower amounts of mucin

• the number of villous goblet cells was decreased 32% relative to wild-type villi

• not observed in mice homozygous for any pair-wise combination of these three genes

• reduced levels of trefoil production, a peptide family critical for mucosal defense and ulcer healing

Genotype
MGI:3512137

cx4

• Allelic Composition: Egf^tm1Dle/Egf^tm1Dle; Ereg^tm1Dwt/Ereg^tm1Dwt; Tgfa^tm1Unc/Tgfa^tm1Unc
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

vision/eye

eyelids open at birth ( J:93327 )

• partial penetrance similar to that in Tgfa^tm1Unc single homozygotes

integument

waved hair ( J:93327 )

• similar to that in Tgfa^tm1Unc single homozygotes