Analysis Tools
mortality/aging
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• die shortly after birth
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limbs/digits/tail
absent radius
(
J:51966
)
absent ulna
(
J:51966
)
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• limb bud formation is initiated, but outgrowth and muscularization of the limbs fail to occur
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• at E10.5 limb bud formation is initiated but severely retarded
• the ectoderm covering the limb buds is not thickened and resembles the ectoderm of the interlimb region
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• muscularization of the limbs fails to occur
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• limb agenesis
(J:114183)
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• forelimb components of the digits, ulna, radius, humerus and the posterior scapula are missing
(J:51966)
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• lack hindlimb components and have a rudimentary iliac bone
(J:51966)
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respiratory system
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• exhibit no evidence for the development of pulmonary circulation
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• few present submucosal glands are located in the proximal position above the first cartilage ring of the trachea
• no submucosal glands are located distally between the tracheal rings
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• the trachea forms but the lungs do not develop
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• lung bud formation is absent at E11.5
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• lung agenesis
(J:114183)
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vision/eye
endocrine/exocrine glands
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• proximal region of colon displays shortened crypts
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• missing submandibular gland, with fibroblastic cells instead of glandular cells occupying the corresponding portion
(J:114183)
• the submandibular salivary gland is entirely absent at E13.5
(J:119849)
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• the submandibular salivary gland is severely hypoplastic at E12.5
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• salivary gland agenesis
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• at P0, basophilic chief cells are found towards the base of the gastric gland
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• at P0, a marked decrease in insulin-expressing cells is observed
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• at E10, a poorly formed Rathke's pouch contains numerous apoptotic (TUNEL+) cells, unlike in wild-type embryos where only a few apoptotic cells are seen at the base of the diverticulum
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• Rathke's pouch is missing at E13.5
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• anterior pituitary agenesis
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• the posterior infundibular recess is still present at E13.5
• by E15.5, development of the posterior pituitary is arrested
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• none of the three lobes are seen at E15.5
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small thymus
(
J:114183
)
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• at P0, the thymus is smaller than normal; however, the medulla-cortex distinction is observed
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• thyroid gland agenesis
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 |
• the epithelial bud of mammary gland 4 penetrates the mammary fat pad but branching is reduced or does not occur
• branching defect is due to the thin fat pad as dissected glands grafted into wild-type mammary fat pads are competent to invade and branch into the wild-type stroma
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• mammary placode 4, but not placodes 1, 2, 3 and 5, is induced and maintained at E13.5 in homozygotes
(J:73434)
• all placodes (1, 2, 3, 5) except 4 are absent along the mammary line
(J:109476)
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• few present submucosal glands are located in the proximal position above the first cartilage ring of the trachea
• no submucosal glands are located distally between the tracheal rings
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• at P0
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• at P0, pancreatic cells are partly replaced by fibroblastic cells
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cardiovascular system
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• no pulmonary arteries are seen in E17.5 embryos
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• orientation of the pulmonary trunk is frequently abnormal in hearts, running transversely, orthogonal to the direction in control hearts
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• no pulmonary veins are seen in E17.5 hearts
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• abnormally positioned atrial appendages
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• the direction of the cardiac apex is frequently abnormal, pointing either to the left in 14%, to the right in 62%, or positioned medially in 20% of mutants, however show normal rightward looping
• 4% show an extreme anterior rightward positioned ventricular apex such that the normally dorsal ventricular surface is apparent in a ventral view
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dextrocardia
(
J:111148
)
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• 62% exhibit a rightward-pointing cardiac apex with situs solitus
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• exhibit no evidence for the development of pulmonary circulation
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adipose tissue
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• development of white adipose tissue is markedly impaired, with significantly reduced cell numbers compared to control tissue
• cell proliferation is reduced in white adipose tissue
• very low lipid accumulation in white adipose tissue is observed
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• white adipose tissue forming the mammary fat pad is very thin
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skeleton
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• tooth dysgenesis
• smaller teeth
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• stem cell loop is missing at E19.5
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small molars
(
J:114183
)
absent radius
(
J:51966
)
absent ulna
(
J:51966
)
|
• the posterior scapula (comprising about 1/3 of the entire scapula) is missing
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digestive/alimentary system
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• at E10.5, gastrointestinal tract tube shows greater diameter reduction than seen in wild-type, at about one third of the length from the proximal end of hindgut
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• epithelium of gastrointestinal tract is absent at a position in proximal region of colon and a position in distal region
• proliferation is reduced in colon at E10.5 relative to wild-type or heterozygous embryos while apoptosis is increased
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• proximal region of colon displays shortened crypts
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• development of the cecum is altered, such that a cecal bud forms but is much smaller at E12.5 and the epithelial layer does not invade the mesenchymal layer
(J:87411)
• at E13.5, ceca show mesenchymal buds that fail to continue development and thus show no progressive elongation of the structure
(J:87411)
• formation of cecum is arrested at E11.5
(J:115048)
|
cecal atresia
(
J:92361
)
|
• 100% show cecal atresia with absence of epithelial and muscular layers
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• at E12.5 there is interruption of the colonic mesenchyme
• at E14.5 the colon is very short compared to wild-type (20% of normal length)
• at E18.5 colon is almost absent; a small pouch adjacent to the cecum represents the residual colon
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absent colon
(
J:115048
)
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• at E18.5 colon is almost absent; a small pouch adjacent to the cecum represents the residual colon
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• at E14.5 the colon is very short compared to wild-type (20% of normal length)
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absent rectum
(
J:92361
)
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• absence of rectum in the pelvis
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• missing submandibular gland, with fibroblastic cells instead of glandular cells occupying the corresponding portion
(J:114183)
• the submandibular salivary gland is entirely absent at E13.5
(J:119849)
|
|
• the submandibular salivary gland is severely hypoplastic at E12.5
|
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• salivary gland agenesis
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• at P0, basophilic chief cells are found towards the base of the gastric gland
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• at P0, smooth muscle layers are absent from the stomach submucosal region
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• at P0
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renal/urinary system
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• development of the ureteric bud is impaired in E14.5 metanephroi
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• at E19.5, the medulla contains fewer renal tubules, loops of Henle, and collecting ducts with more stromal cells
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• at E19.5, the kidney inner medulla is significantly smaller, with an enlarged renal calyx
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• outer medullary dysplasia is already seen at E14.5
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• enlarged renal calyx at E19.5
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small kidney
(
J:114183
)
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• at E16.5, urethra formation is abnormal
• the urethral groove and its proximal connection to the urogenital sinus do not form properly
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• perineal hypospadias
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embryo
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• in E11.5-11.75 embryos, cells of the stratum germinativum are cuboidal rather than cylindrical and formation of the periderm is impaired
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• formation of the periderm is impaired
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• at E10.5 limb bud formation is initiated but severely retarded
• the ectoderm covering the limb buds is not thickened and resembles the ectoderm of the interlimb region
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integument
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• at E19.5, numerous apoptotic (TUNEL+) cells are detected in the hair bulbs and sheath cells, unlike in wild-type hair follicles
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• the epithelial bud of mammary gland 4 penetrates the mammary fat pad but branching is reduced or does not occur
• branching defect is due to the thin fat pad as dissected glands grafted into wild-type mammary fat pads are competent to invade and branch into the wild-type stroma
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• mammary placode 4, but not placodes 1, 2, 3 and 5, is induced and maintained at E13.5 in homozygotes
(J:73434)
• all placodes (1, 2, 3, 5) except 4 are absent along the mammary line
(J:109476)
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• elongation of hair shafts is rarely observed at P0
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• dysgenesis of hair follicles
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• growth of hair bulbs appears disrupted at P0
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muscle
| N |
• all untreated mutant mice develop fully formed, well-muscularized diaphragms despite lung agenesis
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• muscularization of the limbs fails to occur
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• a portion of mutant embryos exposed to a combination of nitrofen, bisdiamine, and SB-210661 teratogens on E8 develop posterolateral left-sided diaphragmatic hernias, indicating that lung tissue is not required for the induction of diaphragmatic defects
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cellular
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• at E19.5, numerous apoptotic (TUNEL+) cells are detected in the hair bulbs and sheath cells, unlike in wild-type hair follicles
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craniofacial
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• tooth dysgenesis
• smaller teeth
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• stem cell loop is missing at E19.5
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small molars
(
J:114183
)
hearing/vestibular/ear
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• inner ear dysgenesis
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• at E10.5, a smaller otic capsule is observed
• however, the endolymphatic duct is formed
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hematopoietic system
small thymus
(
J:114183
)
|
• at P0, the thymus is smaller than normal; however, the medulla-cortex distinction is observed
|
immune system
small thymus
(
J:114183
)
|
• at P0, the thymus is smaller than normal; however, the medulla-cortex distinction is observed
|
nervous system
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• at E10, a poorly formed Rathke's pouch contains numerous apoptotic (TUNEL+) cells, unlike in wild-type embryos where only a few apoptotic cells are seen at the base of the diverticulum
|
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• Rathke's pouch is missing at E13.5
|
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• anterior pituitary agenesis
|
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• the posterior infundibular recess is still present at E13.5
• by E15.5, development of the posterior pituitary is arrested
|
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• none of the three lobes are seen at E15.5
|
growth/size/body
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• tooth dysgenesis
• smaller teeth
|
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• stem cell loop is missing at E19.5
|
small molars
(
J:114183
)
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| intestinal atresia | DOID:10486 | J:92361 | ||
