Mouse Genome Informatics
hm1
    Shhtm1Amc/Shhtm1Amc
involves: 129/Sv * C57BL/6J * CBA/J
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• none of the homozygotes surviving to term live beyond this time
• only ~50% of homozygotes survive to term

digestive/alimentary system
• at 18.5 dpc, homozygotes display a smaller gastrointestinal tract relative to wild-type
• at 18.5 dpc, all homozygotes have an imperforate anus
• at 18.5 dpc, all homozygotes display an obvious malrotation of the gut, in the absence of reversions in gut situs
• at 18.5 dpc, the mutant esophagus tissue is reduced and fused to the trachea
• at 18.5 dpc, the mutant trachea and esophagus are fused to form a fistula-like fusion of the alimentary and respiratory tract
• at 18.5 dpc, the mutant colon ends in a blind dilation that is not fused to the surface ectoderm; however, no aganglionic colon is observed
• at 18.5 dpc, homozygotes show a 21% reduction in thickness of the circular smooth muscle layer along the small intestine; however, no intestinal dilation is observed
• at 18.5 dpc, 67% of homozygotes display occlusion of the duodenum by overgrown villi, resembling duodenal stenosis
• at 18.5 dpc, the mutant glandular epithelium displays histologic features that resemble intestinal metaplasia
• at 18.5 dpc, all homozygotes display a significant overgrowth of stomach epithelium, in spite of normal rates of cell proliferation in the stomach
• at 18.5 dpc, all homozygotes exhibit intestinal transformation of the stomach epithelium

respiratory system
• poorly vascularized airways
• at 18.5 dpc, the mutant trachea and esophagus are fused to form a fistula-like fusion of the alimentary and respiratory tract
• in mutant trachea, the layer of smooth muscle that normally lines the proximal epithelium is absent
• although left and right buds form, mutant lungs fail to undergo lobation or subsequent extensive branching
• at 12.5 dpc, mutant lungs fail to branch or display one abnormally positioned branch point
• in organ culture, mutant lungs fail to grow or branch extensively; bronchial mesenchyme cells detach from the endodermal epithelium
• by 18.5 dpc, only a few air sacs are present
• mutant lungs fail to undergo lobation
• at 18.5 dpc, homozygotes display a rudimentary respiratory organ with a few large, poorly vascularized airways
• in mutant trachea, cartilaginous rings are present but appear disorganized

muscle
• at 18.5 dpc, homozygotes show a 21% reduction in thickness of the circular smooth muscle layer along the small intestine
• in mutant trachea, the layer of smooth muscle that normally lines the proximal epithelium is absent

growth/size/body
• at 18.5 dpc, mutant embryos have an overall reduced size relative to wild-type embryos

endocrine/exocrine glands
• at 18.5 dpc, 85% of homozygotes exhibit an annular pancreas

nervous system
• at 18.5 dpc, homozygotes show excessive and abnormally located neurons that differentiate under the epithelium and into the villi

skeleton
• in mutant trachea, cartilaginous rings are present but appear disorganized

integument
• at 18.5 dpc, mutant hair follicles at stage 1-2 show a 40% decline in keratinocyte proliferation relative to wild-type, with no difference observed in apoptosis
• skin grafts of mutant skin (epidermis and dermis) transplanted onto nude mice generate hairless, pigmented skin
• some keratinized pigmented material resembling hair matrix is present, but no hair is formed
• skin grafts of mutant skin transplanted onto nude mice show abnormal ingrowth of the epidermis and consequently aberrant morphogenesis of the hair shaft
• at 15.5 dpc, mutant hair follicles form a smaller hair plug; however, epidermal expansion into the dermis and dermal condensation of mesenchyme at the base of the hair plug occur normally
• at 15.5 dpc, wild-type hair follicles have progressed to stage 2, whereas mutant follicles at still at stage 1 or 0
• skin grafts of mutant skin transplanted onto nude mice exhibit giant disorganized hair-bud-like structures, some with hair-shaft-like material, in the vicinity of epidermis
• homozygotes display delayed hair folliculoenesis: embryonic follicles are arrested shortly after induction and fail to progress beyond stage 2
• at 18.5 dpc, mutant hair follicles at stage 1-2 show a 40% decline in keratinocyte proliferation relative to wild-type; no difference is observed in apoptosis
• mutant hair follicles fail to initiate development of the inner root sheath from the hair matrix (stages 3-5)
• by 18.5 dpc, homozygotes show a severe reduction in the number of induced hair follicles relative to wild-type mice
• mutant hair buds fail to exhibit an obvious polarity; in contrast, wild-type follicles show a typical polarized development along the anterior-posterior axis
• skin grafts of mutant skin transplanted onto nude mice exhibit a reduced dermal fat layer
• mutant skin displays only a rudimentary dermal papilla, indicating abnormal epithelial-mesenchymal interactions
• skin grafts of mutant skin transplanted onto nude mice display hyperplasia and abnormal keratin expression in interfollicular epidermis
• skin grafts of mutant skin transplanted onto nude mice exhibit a thickened epidermis with large disorganized ingrowths

cardiovascular system
• poorly vascularized airways

cellular
• at 18.5 dpc, mutant hair follicles at stage 1-2 show a 40% decline in keratinocyte proliferation relative to wild-type, with no difference observed in apoptosis


Mouse Genome Informatics
hm2
    Shhtm1Amc/Shhtm1Amc
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
embryogenesis

nervous system

skeleton
• all ventral vertebral components are absent


Mouse Genome Informatics
hm3
    Shhtm1Amc/Shhtm1Amc
Not Specified
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• homozygous mutants die shortly after birth

digestive/alimentary system
• a single tracheal-esophageal tube lacking any cartilaginous rings is seen
• this tube is lined with stratified squamous epithelium dorsally and columnar airway epithelium ventrally
• reduced stomach size, particularly in the fore-stomach, at E12.5

respiratory system
• a single tracheal-esophageal tube lacking any cartilaginous rings is seen
• this tube is lined with stratified squamous epithelium dorsally and columnar airway epithelium ventrally
• branching morphogenesis is impaired with the single tracheal-esophageal tube connected to the proximal and peripheral lung structures
• lungs are severely hypoplastic
• the anterior closed pharynx connects to a posteroir bilobed lung in which the central airway is surrounded only by rudimentary peripheral saccules
• peripheral tubules are absent
• the pharynx is closed anteriorly
• the cartilaginous rings that normally surround the trachea are absent

skeleton
• the cartilaginous rings that normally surround the trachea are absent


Mouse Genome Informatics
hm4
    Shhtm1Amc/Shhtm1Amc
STOCK Shhtm1Amc/J
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
digestive/alimentary system
• at E13.5 and E15.5, homozygotes show a severely reduced, dysplastic remnant of the submandibular salivary gland (SMG)
• at E18.5, homozygotes display a slightly larger but severely pedomorphic dysplastic SMG consisting of largely undifferentiated epithelium with very few branches surrounded by undifferentiated mesenchyme (reminiscent of the Pseudoglandular stage at ~E14)
in vitro, Pseudoglandular (E14) stage SMG primordia cultured in the presence of Shh show a ~2-fold increase in epithelial branching compared with Initial Bud (E13) stage primordia, indicating a stage-specific difference in Shh-stimulated branching
• cyclopamine-treated explants show a marked reduction in branching and epithelial cell proliferation; notably FGF8-supplemented explants exhibit a significant 58% increase in branching morphogenesis compared with cyclopamine treatment alone

endocrine/exocrine glands
• at E13.5 and E15.5, homozygotes show a severely reduced, dysplastic remnant of the submandibular salivary gland (SMG)
• at E18.5, homozygotes display a slightly larger but severely pedomorphic dysplastic SMG consisting of largely undifferentiated epithelium with very few branches surrounded by undifferentiated mesenchyme (reminiscent of the Pseudoglandular stage at ~E14)
in vitro, Pseudoglandular (E14) stage SMG primordia cultured in the presence of Shh show a ~2-fold increase in epithelial branching compared with Initial Bud (E13) stage primordia, indicating a stage-specific difference in Shh-stimulated branching
• cyclopamine-treated explants show a marked reduction in branching and epithelial cell proliferation; notably FGF8-supplemented explants exhibit a significant 58% increase in branching morphogenesis compared with cyclopamine treatment alone


Mouse Genome Informatics
ht5
    Shhtm1Amc/Shhtm1.1Rseg
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
embryogenesis
N
• while organ size is reduced to various degrees, all organs are present and correctly localized unlike in Shh-null mice

growth/size/body
• body weight of mice is greatly reduced compared to controls

nervous system
• brain weight is less than controls
• olfactory bulb is disproportionately smaller than controls
• cerebella is 50% smaller than controls, which is disproportionately smaller compared to other organs

vision/eye
• eyes are small but are well-spaced unlike Shh-null mice that have improperly spaced eyes


Mouse Genome Informatics
ht6
    Shhtm1Amc/Shhtm2Amc
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
normal phenotype
• compound heterozygotes for Shhtm1Amc and Shhtm2Amc are viable and fertile with no discernible phenotype


Mouse Genome Informatics
ht7
    Shhtm1.1Dje/Shhtm1Amc
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * FVB/N
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 80% of mice fail to gain weight and die by 7 days of age
• 20% survive to adulthood

growth/size/body
• normal weight at birth
• 80% fail to gain weight after birth and die by 7 days of age
• the 20% who survive remain remain small, 33% of normal weight

behavior/neurological
N
• normal suckling response
• dead pups often have milk in their stomach
• well coordinated motor control

homeostasis/metabolism
N
• normal blood glucose


Mouse Genome Informatics
cn8
    Gt(ROSA)26Sortm5(Etv4/en,-GFP)Amc/Gt(ROSA)26Sor+
Shhtm1Amc/Shhtm2Amc
Tg(Prrx1-cre)1Cjt/0

involves: 129 * C57BL/6 * CBA * SJL/J * Swiss Webster
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
limbs/digits/tail
• at P1, digits appear posteriorized comparing relative digit length and phalanx morphology with that of controls Shhtm1Amc/Shhtm2Amc Tg(Prrx1-cre)1Cjt mice
• however, mice have the same number of digits as in Shhtm1Amc/Shhtm2Amc Tg(Prrx1-cre)1Cjt mice


Mouse Genome Informatics
cn9
    Disp1icb/Disp1icb
Shhtm1Amc/Shhtm5Amc
Tg(Sox2-cre)1Amc/0

involves: 129/Sv * C57BL/6J * SWR
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• compound mutants die around birth unlike Disp1 single homozygotes which die before E9.5

craniofacial