Mouse Genome Informatics
cn1
    Sox9tm1Gsr/Sox9tm1Gsr
involves: 129P2/OlaHsd * 129S1/SvImJ * NMRI
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
renal/urinary system
N
• bladder morphology is normal (J:166547)
• 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
• at E18.5
• bilateral in 94% of mice at E18.5
• unilateral in 6% of mice at E18.5
• 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

limbs/digits/tail
• at E18.5, mice exhibit rudimentary limbs compared with wild-type mice
• at E18.5, mice exhibit tail truncation compared with wild-type mice

embryogenesis
• at E18.5, mice exhibit shortened body axis compared with wild-type mice


Mouse Genome Informatics
cn2
    Sox9tm1Gsr/Sox9tm1Gsr
Tg(SFTPC-rtTA)5Jaw/0
Tg(tetO-cre)1Jaw/0

involves: 129 * 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
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) (J:95910)

homeostasis/metabolism
N
• mice treated with doxycycline from E0.5 display normal survival and repair after hyperoxia-induced lung injury (95% oxygen for 3 days) relative to control littermates (J:95910)


Mouse Genome Informatics
cn3
    Sox9tm1Gsr/Sox9tm1Gsr
Shhtm1(EGFP/cre)Cjt/Shh+

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 1 of 3 pups died at birth
• the 2 pups that survived past birth had to be euthanized by P7

respiratory system
• 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
• 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
• noticeable by E14.5 and more significant by E16.5
• develop large, cyst-like structures at the distal epithelial branch tips that are the result of larger, rounder branch tips
• pups that survive birth have difficulty breathing

cellular
• apparent precocious differentiation of distal tip progenitor cells into type 2 alveolar cells at E14.5
• migration of epithelial cells from cultured E12.5 lung buds is decreased compared to controls
• significant decrease in total lung epithelial cell proliferation at E14.5 resulting from a decrease in proliferation of the distal tip epithelium


Mouse Genome Informatics
cn4
    Sox9tm1Gsr/Sox9tm1Gsr
Krt19tm1(cre)Mmt/Krt19+

involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• recover only about 1/8 of the expected number of embryos after E11.5, however some survive up to E15.5

reproductive system
• Leydig cells do not form
• failure of testis differentiation is apparent at E12.5
• lack of testis cord formation
• 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

cardiovascular system

skeleton
• display a reduction in all cartilage anlagen

endocrine/exocrine glands
• Leydig cells do not form
• failure of testis differentiation is apparent at E12.5
• lack of testis cord formation

embryogenesis
• absence of Mullerian duct regression in males
• display a reduction in cranial neural crest cell-derived tissue

nervous system
• display a reduction in cranial neural crest cell-derived tissue


Mouse Genome Informatics
cn5
    Sox9tm1Gsr/Sox9tm1Gsr
Tg(Col2a1/Acan-rtTA,tetO-cre)#Vlf/0

involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• with doxycycline treatment from E15.5 on, columnar zones are shortened in growth plates of mutants
• with doxycycline treatment from E15.5 onward, severe dwarfism results
• endochondral bones stop elongating by E17.5 with doxycycline treatment from E15.5 onward
• 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


Mouse Genome Informatics
cn6
    Sox9tm1Gsr/Sox9+
Tg(Pdx1-cre)6Cvw/0

involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * CBA * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
N
• despite islet cell hypoplasia, pancreas size, weight, morphology and pancreatic exocrine differentiation are normal at E18.5 (J:141017)
• at E18.5, the numbers of polypeptide producing cells are reduced compared to wild-type mice
• at E18.5, alpha cell mass is reduced 55% compared to in wild-type mice
• at E18.5, beta cell mass is reduced 57% compared to in wild-type mice
• however, beta cell differentiation is normal
• at E18.5, delta cell numbers are decreased compared to in wild-type mice
• mice exhibit islet hyperplasia
• 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
• pancreatic glucagons is reduced 34.9% compared to in wild-type
• pancreatic insulin production is decreased 44% compared to in wild-type mice

digestive/alimentary system
N
• despite islet cell hypoplasia, pancreas size, weight, morphology and pancreatic exocrine differentiation are normal at E18.5 (J:141017)

homeostasis/metabolism
• pancreatic glucagons is reduced 34.9% compared to in wild-type
• pancreatic insulin production is decreased 44% compared to in wild-type mice

Mouse Models of Human Disease
OMIM IDRef(s)
Campomelic Dysplasia 114290 J:141017


Mouse Genome Informatics
cn7
    Sox9tm1Gsr/Sox9+
Tg(Pax3-cre)1Joe/0

involves: 129P2/OlaHsd * C57BL/6 * NMRI * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
renal/urinary system
• bilateral in 4% of mice at E18.5
• unilateral in 25% of mice at E18.5
• in 5% of mice t E18.5


Mouse Genome Informatics
cn8
    Sox9tm1Gsr/Sox9tm1Gsr
Tg(Pax3-cre)1Joe/0

involves: 129P2/OlaHsd * C57BL/6 * NMRI * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
renal/urinary system
• 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
• at E18.5
• bilateral in 28% of mice at E18.5
• unilateral in 34% of mice at E18.5
• in 72% of mice at E18.5
• cultured ureter explants from E15.5 embryos exhibit only mediocre elongation and weak peristaltic activity compared with wild-type explants

limbs/digits/tail
• at E18.5, mice exhibit rudimentary limbs compared with wild-type mice
• at E18.5, mice exhibit tail truncation compared with wild-type mice

embryogenesis
• at E18.5, mice exhibit shortened body axis compared with wild-type mice


Mouse Genome Informatics
cn9
    Sox9tm1Gsr/Sox9tm1Gsr
Tg(Tek-cre)1Ywa/0

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

cardiovascular system
• in the atrioventricular canal, there is malalignment of the atrial septum, although the septum does meet the endocardial cushions in more distal areas
• 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%
• endocardial cushions within the outflow tract appear grossly reduced in size
• incomplete formation of the atrial septum
• defects in valve maturation
• atrioventricular valve primordia do not form at E13.5
• mutants exhibit increased blood pooling

homeostasis/metabolism


Mouse Genome Informatics
cn10
    Sox9tm1Gsr/Sox9tm1Gsr
Tg(Col2a1-cre)1Bhr/0

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

cardiovascular system
• width of the interventricular septum is increased
• heart valve leaflets are thickened at E18.5
• abnormal organization of the stratified extracellular matrix layers within the valve leaflets

respiratory system
• respiratory defects


Mouse Genome Informatics
cn11
    Sox9tm1Gsr/Sox9+
Tg(Col2a1-cre)1Bhr/0

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• from 3 months of age, heart valve leaflets are thickened
• 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
• 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
• 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
• adult mitral valves show calcium deposits