All Phenotypes Errfi1<tm1.1Jwj> MGI Mouse

premature death ( J:129106 )

• most mice die prior to 6 months of age

postnatal lethality, incomplete penetrance ( J:129106 , J:153715 )

• 50% fewer mice are present at weaning than expected (J:129106)

• only 9.3% and 12.1% (instead of expected 25%) of homozygotes are present at P3 and P28, respectively (J:153715)

• no significant changes in Mendelian ratios are observed prior to birth (E15.5-E18.5) (J:153715)

• the luminal and glandular epithelium display cellular stratification and enlarged, elongated nuclei compared to in wild-type mice

endometrium hyperplasia ( J:129106 )

increased uterus weight ( J:129106 )

• the uterus of mice surviving to 9 months is increased in size and weight compared to wild-type mice

abnormal joint morphology ( J:129106 )

• mice develop joint degeneration

• mice develop enlargement and deformity in the knee, ankle and temporomandibular joints

• joints exhibit abnormally rough surfaces and narrowed joint space

• multiple cysts filled with fibroblast-like cells form in the subchondrial regions

increased skin papilloma incidence ( J:129106 )

epidermal hyperplasia ( J:129106 )

thick skin ( J:129106 )

• mice develop thick tail and footpad skin

increased skin papilloma incidence ( J:129106 )

abnormal eating behavior ( J:153715 )

• most pups are less capable of feeding

absent gastric milk in neonates ( J:153715 )

• most pups lack milk in their stomachs

decreased locomotor activity ( J:153715 )

• most pups are less active than normal

decreased birth weight ( J:153715 )

• average birth weight is only 77% of that in control neonates

cyanosis ( J:153715 )

• many pups become cyanotic shortly before death

• however, lungs are well inflated at birth, as shown by the floating lung assay

abnormal lung morphology ( J:153715 )

• at 3 months, mice display features of chronic obstructive pulmonary disease with an increase in macrophage invasion and mucous cell metaplasia

• however, no asthma (airway contraction) is observed

abnormal lung vasculature morphology ( J:153715 )

• at E15.5, lung blood vessels are rarely discernible, unlike in wild-type lungs

• at P3, PECAM1 staining is significantly reduced, the endothelium is deeply embedded in the mesenchyme and appears discontinuous with the alveolar surface, unlike in wild-type lungs

• at P3, alpha-SMA immunostaining indicates poorly developed blood vessels, unlike in wild-type lungs

• at P3, the number of proliferating cells is reduced by 66% in the blood vessels relative to wild-type lungs

• at P3, reduced lung vascularization is associated with decreased angiogenetic gene expression

abnormal lung development ( J:153715 )

• mice exhibit defects during mid-to-late stages of lung development, including airway over-branching, alveolar type II cell hyperplasia, arrested alveolarization and reduced vascularization

• at P3, the number of proliferating cells is increased 3-fold in the airways, but reduced by 66% in the blood vessels relative to wild-type lungs

• at P3, apoptotic cells are frequently detected in the airway epithelium, blood vessels, mesenchyme and alveolar septa, unlike in wild-type lungs

impaired lung alveolus development ( J:153715 )

• at E18.5, the mean number of primitive alveoli per terminal airway is reduced by ~50% relative to that in wild-type lungs

• at P3, the mean number of secondary septa per alveolar sac is reduced by ~50% relative to that in wild-type lungs

• by P3, only smaller and compressed alveoli are observed and the mesenchyme remains thick, unlike in wild-type lungs

abnormal lung interstitium morphology ( J:153715 )

• at 3 months, a significant increase in extracellular matrix deposition is noted around the bronchi, around the blood vessels, in the alveolar interstitia and in the pleural membranes

small lung ( J:153715 )

• at E15.5, mutant lungs are significantly smaller than wild-type lungs

overexpanded pulmonary alveolus ( J:153715 )

• at 3 months, alveolar spaces are enlarged and mean alveolar chord length is significantly increased relative to that in wild-type lungs

pale lung ( J:153715 )

• at E15.5, mutant lungs are paler than wild-type lungs

abnormal respiratory epithelium morphology ( J:153715 )

• at P3, large airways appear over-branched while small airways show an irregular morphology with hyperplastic CCSP-positive epithelium

• at 3 months, papillary hyperplastic proliferation is observed in the airway epithelium

bronchiolar epithelial hyperplasia ( J:153715 )

• at P3, small airways display hyperplastic Clara cell secretory protein (CCSP)-positive epithelium

bronchial epithelial hyperplasia ( J:153715 )

• at P3, proliferating cells are frequently found in the bronchial epithelium, unlike in wild-type lungs

increased type II pneumocyte number ( J:153715 )

• at P3, pro-SP-C staining of distal lungs indicates alveolar type II cell hyperplasia

• multiple alveolar type II cells are observed at the antrum to the alveoli

lung epithelium hyperplasia ( J:153715 )

• at P3, lung epithelial hyperplasia is associated with increased EGF signaling