Phenotypes associated with this allele

• Allele Symbol: Areg^tm1Dle
• Allele Name: targeted mutation 1, David C Lee
• Allele ID: MGI:2176531
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Areg^tm1Dle/Areg^tm1Dle	involves: 129P2/OlaHsd * C57BL/6	MGI:2176533
cx2	Areg^tm1Dle/Areg^tm1Dle Egf^tm1Dle/Egf^tm1Dle Tgfa^tm1Unc/Tgfa^tm1Unc	involves: 129P2/OlaHsd * C57BL/6	MGI:2176534

Genotype
MGI:2176533

hm1

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

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

cardiovascular system

cardiovascular system phenotype ( J:60750 )

N • normal heart valves

endocrine/exocrine glands

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 an 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; however, lactation improved with aged mothers

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 an irregular, compact alveolar morphology observed

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 an 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; however, lactation improved with aged mothers

Genotype
MGI:2176534

cx2

• 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