All Phenotypes Nkx2-1<tm1Shk> MGI Mouse

neonatal lethality, complete penetrance ( J:30559 )

• mice survive throughout a normal-length gestation but die at birth

endocrine/exocrine gland phenotype ( J:30559 )

N	• normal parathyroid gland

abnormal adrenal cortex morphology ( J:30559 )

• the cells in the zona fasciculata of the adrenal cortex have an underdeveloped appearance with very little cytoplasm

abnormal adenohypophysis development ( J:50517 )

• a Rathke's pouch (anterior pituitary primordium) is initially formed but is subsequently eliminated through apoptosis

abnormal Rathke's pouch apoptosis ( J:50517 )

• at E10.5, Rathke's pouch contains many apoptotics cells, unlike in wild-type controls

abnormal Rathke's pouch development ( J:50517 )

• only a thin, rudimentary pouch is formed

• at E10.5, the pouch remains single-layered, fails to differentiate, and is subsequently eliminated through apoptosis

absent pituitary infundibular stalk ( J:50517 )

• at E10.5, the infundibulum of the hypothalamus is absent

absent pituitary gland ( J:30559 )

• the anterior, intermediate, and posterior pituitary are missing

abnormal thyroid gland development ( J:110629 )

• at E10.5, a thyroid primordium is identified but is much smaller than normal and is still connected to the pharyngeal floor via the thyroglossal duct; mutant thyroid primordial cells are subsequently eliminated through apoptosis

absent thyroid gland ( J:30559 )

• the thyroid gland is entirely absent as early as E12 or E13

abnormal Leydig cell morphology ( J:80472 )

• at E18.5, mutant Leydig cells appear well-differentiated but are consistently much smaller in size, with smaller mitochondria and proportion of smooth endoplasmic reticulum than seen in controls

• mutant fetal Leydig cells show all ultrastructural features of steroidogenic cells, despite a 90-95% reduction in Leydig cell steroid content

decreased testis weight ( J:80472 )

• at E18.5, testis weights of male homozygotes are 20% lower than those of wild-type or heterozygous controls

decreased testes secretion ( J:80472 )

• at E18.5, the testosterone content of homozygous mutant testes (13.5 +/- 2.4 pg/gonad) is severely reduced relative to that in heterozygous (165 +/- 22.5 pg) and wild-type (234 +/- 37.3 pg) littermates

abnormal pulmonary circulation ( J:54641 )

• mutant embryos exhibit abnormal cardiopulmonary circulation

abnormal lung development ( J:30559 , J:54641 , J:110629 )

• lung development is arrested around E12.5-E13 (J:30559)

• mutant lungs are developmentally arrested prior to E15, as indicated by RT-PCR analysis of Vegf transcripts (J:54641)

• lung morphogenesis is arrested at the onset of the pseudoglandular period of lung development, resulting in the absence of distal structures (J:54641)

• the lung primordium is initially specified; however, subsequent morphogenesis and differentiation is abrogated in the absence of increased apoptosis in the lung epithelium (J:110629)

impaired branching involved in bronchus morphogenesis ( J:30559 , J:54641 )

• progressive development of the lower bronchial tree does not occur (J:30559)

• no branching of lobar bronchi into segmental bronchi is observed (J:30559)

• at E12, mutant lungs fail to undergo normal branching morphogenesis beyond the main-stem bronchi (J:54641)

• at E18, at the end of each main-stem bronchus, mutant lungs consist of translucent semiamorphous cystic structures rather than a highly refined branched structure (J:54641)

abnormal lung epithelium morphology ( J:54641 )

• expression of Bmp4 in the embryonic lung epithelium is severely reduced providing a potential mechanism for the "dilated sac" phenotype

abnormal bronchus epithelium morphology ( J:30559 )

• abnormal bronchial epithelium, including multiple layers of cells, apparent syncytial cells, and hyperchromatic cells

abnormal type II pneumocyte morphology ( J:54641 )

• pulmonary-specific epithelial cell differentiation is blocked, as shown by the absence of pulmonary surfactant protein gene expression

absent type II pneumocytes ( J:54641 )

• at E18, no cells of cuboidal epithelial phenotype are observed in mutant lungs

decreased lung weight ( J:54641 )

• mutant lungs are smaller in size by 50-60% wet weight

pulmonary hypoplasia ( J:30559 , J:110629 )

• mutant lungs are severely hypoplastic but still present in neonates (J:110629)

abnormal pulmonary alveolar parenchyma morphology ( J:30559 )

• absence of lung parenchyma

abnormal bronchus morphology ( J:30559 )

• rudimentary bronchial tree with some mice showing many cystic branches of bronchus

abnormal pleural cavity morphology ( J:30559 , J:54641 )

• dilated sac-like structures exist in the pleural cavity, indicating the presence of a rudimentary bronchial tree (J:30559)

• the pleural space is filled with fluid of unknown origin (J:54641)

abnormal trachea morphology ( J:54641 )

• at E18, the tracheal portion of mutant lungs is significantly foreshortened and larger in diameter

tracheoesophageal fistula ( J:54641 )

• at E18, a common lumen (i.e. a single tracheoesophageal tube) connects the pharynx to severely dysplastic lungs and then through a normal esophagus to the stomach

abnormal tracheal cartilage morphology ( J:54641 )

• at E18, the cranial portion of the common lumen displays features of both trachea and esophagus; however, the shape and number of tracheal cartilage rings is significantly reduced

decreased tracheal cartilage ring number ( J:54641 )

• at E18

abnormal forebrain morphology ( J:30559 )

• defects within the ventral region of the forebrain; the ventral region is not well separated and appears fused in the midline

abnormal diencephalon morphology ( J:30559 )

• unidentified thick crossing fibers, distinct from the optic tract, are seen on the floor of the diencephalon

abnormal adenohypophysis development ( J:50517 )

• a Rathke's pouch (anterior pituitary primordium) is initially formed but is subsequently eliminated through apoptosis

abnormal Rathke's pouch apoptosis ( J:50517 )

• at E10.5, Rathke's pouch contains many apoptotics cells, unlike in wild-type controls

abnormal Rathke's pouch development ( J:50517 )

• only a thin, rudimentary pouch is formed

• at E10.5, the pouch remains single-layered, fails to differentiate, and is subsequently eliminated through apoptosis

absent pituitary infundibular stalk ( J:50517 )

• at E10.5, the infundibulum of the hypothalamus is absent

absent pituitary gland ( J:30559 )

• the anterior, intermediate, and posterior pituitary are missing

abnormal hypothalamus morphology ( J:30559 )

• the ventromedial and dorsomedial nuclei are reduced in size and are fused in the midline

• the premammillary nucleus and the arcuate nucleus are not developed

• anterior hypothalamic nucleus is slightly reduced in size and the anterobasal nucleus is found on the floor of the diencephalon

• in the posterior hypothalamus, the mammillary body and the supramammillary nucleus are absent

abnormal ventromedial hypothalamic nucleus morphology ( J:30559 )

• the ventromedial nuclei are reduced in size and fused in the midline

decreased ventromedial hypothalamic nucleus size ( J:30559 )

abnormal thoracic cavity morphology ( J:54641 )

• the thoracic cavity is only partially filled by hypoplastic lungs

decreased fetal weight ( J:30559 )

• weight is about 85% of controls at E19.5

reproductive system phenotype ( J:80472 )

N	• at E18.5, homozygotes of both sexes display normal external and internal genitals with the expected sex differences observed in anogenital distances • at E18.5, male homozygotes exhibit normal transabdominal testicular descent and regression of the Mullerian ducts