Phenotypes associated with this allele
Allelic Composition |
Sox9tm1Gsr/Sox9tm1Gsr
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Genetic Background |
involves: 129P2/OlaHsd * 129S1/SvImJ * NMRI |
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sox9tm1Gsr mutation
(2 available);
any
Sox9 mutation
(32 available)
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renal/urinary system
N |
• bladder morphology is normal
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• ureters are deficient in smooth muscle cells compared to in wild-type mice
• the composition of ureter extracellular matrix is altered compared to in wild-type mice
• however, ureteric mesenchyme condensation and differentiation are normal
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• ureters are deficient in smooth muscle cells compared to in wild-type mice
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• bilateral in 94% of mice at E18.5
• unilateral in 6% of mice at E18.5
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• cultured ureter explants from E15.5 embryos loses cohesive structure and disperses unlike wild-type explants
• however, cell proliferation and apoptosis of ureteric mesenchyme are normal
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limbs/digits/tail
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• at E18.5, mice exhibit rudimentary limbs compared with wild-type mice
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• at E18.5, mice exhibit tail truncation compared with wild-type mice
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embryo
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• at E18.5, mice exhibit shortened body axis compared with wild-type mice
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respiratory system
N |
• mice treated with doxycycline from E0.5 display normal postnatal survival and normal lung morphology with no detectable changes in the cellular differentiation or development of peripheral lung epithelium at all stages analyzed (E12.5 to adulthood)
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homeostasis/metabolism
mortality/aging
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• 1 of 3 pups died at birth
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• the 2 pups that survived past birth had to be euthanized by P7
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respiratory system
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• develop large, cyst-like structures at the distal epithelial branch tips that are the result of larger, rounder branch tips
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• cultured lungs from E12.5 embryos show a significant reduction in branching
• branch tips are larger and rounder and lead to large open spaces in the lung
• significant decrease in total lung epithelial cell proliferation at E14.5 resulting from a decrease in proliferation of the distal tip epithelium
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• distal epithelial tips show a range of defects including absence of microvilli, apical membranous blebs and disrupted cell-cell adhesion
• the basal epithelial surface is not uniform and many cells have a rounded appearance with membranous blebs projecting into the subcellular space
• the extracellular matrix and stabilized tubulin appear disrupted at the basal surfaces
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• noticeable by E14.5 and more significant by E16.5
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• pups that survive birth have difficulty breathing
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cellular
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• apparent precocious differentiation of distal tip progenitor cells into type 2 alveolar cells at E14.5
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• migration of epithelial cells from cultured E12.5 lung buds is decreased compared to controls
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• significant decrease in total lung epithelial cell proliferation at E14.5 resulting from a decrease in proliferation of the distal tip epithelium
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growth/size/body
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• develop large, cyst-like structures at the distal epithelial branch tips that are the result of larger, rounder branch tips
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Krt19tm1(cre)Mmt mutation
(0 available);
any
Krt19 mutation
(19 available)
Sox9tm1Gsr mutation
(2 available);
any
Sox9 mutation
(32 available)
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mortality/aging
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• recover only about 1/8 of the expected number of embryos after E11.5, however some survive up to E15.5
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reproductive system
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• failure of testis differentiation is apparent at E12.5
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• lack of testis cord formation
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• Leydig cells do not form
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• XY gonads up to E15.5 show immediate complete sex reversal as indicated by the expression of early ovary-specific markers and lack of testis cord and Leydig cell formation
• 2 of 11 embryos form a completely sex-reversed gonad on one side and an ovotestis on the contralateral side
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cardiovascular system
skeleton
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• display a reduction in all cartilage anlagen
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endocrine/exocrine glands
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• failure of testis differentiation is apparent at E12.5
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• lack of testis cord formation
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• Leydig cells do not form
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embryo
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• absence of Mullerian duct regression in males
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• display a reduction in cranial neural crest cell-derived tissue
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nervous system
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• display a reduction in cranial neural crest cell-derived tissue
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sox9tm1Gsr mutation
(2 available);
any
Sox9 mutation
(32 available)
Tg(Col2a1/Acan-rtTA,tetO-cre)#Vlf mutation
(0 available)
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skeleton
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• with doxycycline treatment from E15.5 on, columnar zones are shortened in growth plates of mutants
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• with doxycycline treatment from E15.5 onward, severe dwarfism results
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• endochondral bones stop elongating by E17.5 with doxycycline treatment from E15.5 onward
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• chondrocytes lose ability to enlarge by E17.5 when doxycycline treatment takes place from E15.5 onward
• columnar cells stop proliferating at a rate 3 times greater than control cells with doxycycline treatment starting at E15.5; number of apoptotic cells in the columnar zone of growth plates is about 28 fold higher and about 5 times higher in the prehypertrophic zone of controls with 2 days of doxycycline treatment
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sox9tm1Gsr mutation
(2 available);
any
Sox9 mutation
(32 available)
Tg(Pdx1-cre)6Cvw mutation
(0 available)
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endocrine/exocrine glands
N |
• despite islet cell hypoplasia, pancreas size, weight, morphology and pancreatic exocrine differentiation are normal at E18.5
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• at E18.5, the numbers of polypeptide producing cells are reduced compared to wild-type mice
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• at E18.5, alpha cell mass is reduced 55% compared to in wild-type mice
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• at E18.5, beta cell mass is reduced 57% compared to in wild-type mice
• however, beta cell differentiation is normal
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• at E18.5, delta cell numbers are decreased compared to in wild-type mice
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• mice exhibit islet hyperplasia
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• the number of pancreatic endocrine progenitor cells is 2-fold less than in wild-type mice due to decreased cell proliferation of endocrine progenitor cells
• however, exocrine progenitor cells are normal in number and proliferation
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• pancreatic glucagons is reduced 34.9% compared to in wild-type
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• pancreatic insulin production is decreased 44% compared to in wild-type mice
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digestive/alimentary system
N |
• despite islet cell hypoplasia, pancreas size, weight, morphology and pancreatic exocrine differentiation are normal at E18.5
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homeostasis/metabolism
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sox9tm1Gsr mutation
(2 available);
any
Sox9 mutation
(32 available)
Tg(Pax3-cre)1Joe mutation
(0 available)
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renal/urinary system
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• bilateral in 4% of mice at E18.5
• unilateral in 25% of mice at E18.5
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sox9tm1Gsr mutation
(2 available);
any
Sox9 mutation
(32 available)
Tg(Pax3-cre)1Joe mutation
(0 available)
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renal/urinary system
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• cultured ureter explants from E15.5 embryos exhibit only mediocre elongation and weak peristaltic activity compared with wild-type explants
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• ureters are deficient in smooth muscle cells compared to in wild-type mice
• the composition of ureter extracellular matrix is altered compared to in wild-type mice
• however, ureteric mesenchyme condensation and differentiation are normal
|
|
• ureters are deficient in smooth muscle cells compared to in wild-type mice
|
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• bilateral in 28% of mice at E18.5
• unilateral in 34% of mice at E18.5
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• in 72% of mice at E18.5
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limbs/digits/tail
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• at E18.5, mice exhibit rudimentary limbs compared with wild-type mice
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• at E18.5, mice exhibit tail truncation compared with wild-type mice
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embryo
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• at E18.5, mice exhibit shortened body axis compared with wild-type mice
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muscle
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• cultured ureter explants from E15.5 embryos exhibit only mediocre elongation and weak peristaltic activity compared with wild-type explants
|
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sox9tm1Gsr mutation
(2 available);
any
Sox9 mutation
(32 available)
Tg(Col2a1-cre)1Bhr mutation
(3 available)
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cardiovascular system
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• 75% of mutants, starting at 3 months of age, show mineral deposits in atrioventricular and outflow tract heart valve leaflets compared to 37.5% of controls
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• the atrioventricular valve leaflet area is greater than in controls and is associated with an increase in proteoglycans at the tip of the valve leaflets
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• adult mitral valves show calcium deposits
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• the outflow tract valve leaflet area is greater than in controls and is associated with an increase in proteoglycans at the tip of the valve leaflets
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• from 3 months of age, heart valve leaflets are thickened
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sox9tm1Gsr mutation
(2 available);
any
Sox9 mutation
(32 available)
Tg(Tek-cre)1Ywa mutation
(6 available)
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mortality/aging
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• die between E11.5 and E14.5
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cardiovascular system
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• endocardial cushions within the outflow tract appear grossly reduced in size
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• in the atrioventricular canal, there is malalignment of the atrial septum, although the septum does meet the endocardial cushions in more distal areas
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• endocardial cushions are hypoplastic and fail to elongate and form atrioventricular valve primordia at E13.5
• at E12.5, cell proliferation within the endocardial cushion is reduced by 75%
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• defects in valve maturation
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• atrioventricular valve primordia do not form at E13.5
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• incomplete formation of the atrial septum
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• mutants exhibit increased blood pooling
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homeostasis/metabolism
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sox9tm1Gsr mutation
(2 available);
any
Sox9 mutation
(32 available)
Tg(Col2a1-cre)1Bhr mutation
(3 available)
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mortality/aging
cardiovascular system
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• width of the interventricular septum is increased
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• heart valve leaflets are thickened at E18.5
• abnormal organization of the stratified extracellular matrix layers within the valve leaflets
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respiratory system