Phenotypes associated with this allele

• Allele Symbol: Tg(Nkx2-1-cre)2Sand
• Allele Name: transgene insertion 2, Stewart Anderson
• Allele ID: MGI:3773076
• Summary: 11 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Pten^tm1Hwu/Pten^tm1Hwu Tg(Nkx2-1-cre)2Sand/0	B6.Cg-Pten^tm1Hwu Tg(Nkx2-1-cre)2Sand	MGI:5517706
cn2	Pten^tm1Hwu/Pten^+ Tg(Nkx2-1-cre)2Sand/0	B6.Cg-Pten^tm1Hwu Tg(Nkx2-1-cre)2Sand	MGI:5517709
cn3	Stk3^tm1.1Jav/Stk3^tm1.1Jav Stk4^tm1Kina/Stk4^tm1Kina Tg(Nkx2-1-cre)2Sand/?	involves: 129 * C57BL/6	MGI:5502638
cn4	Dbx1^tm2Jcor/Dbx1^tm1Tmj Tg(Nkx2-1-cre)2Sand/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5697928
cn5	Pten^tm1Hwu/Pten^+ Tg(Nkx2-1-cre)2Sand/0	involves: 129S4/SvJae * BALB/c * C57BL/6	MGI:5517675
cn6	Pten^tm1Hwu/Pten^tm1Hwu Tg(Nkx2-1-cre)2Sand/0	involves: 129S4/SvJae * BALB/c * C57BL/6	MGI:5014514
cn7	Pten^tm1Hwu/Pten^tm1Hwu Tg(Nkx2-1-cre)2Sand/0	involves: 129S4/SvJae * C57BL/6	MGI:4836606
cn8	Yy1^tm2.1Yshi/Yy1^tm2.1Yshi Tg(Nkx2-1-cre)2Sand/0	involves: 129S4/SvJae * C57BL/6J	MGI:5902325
cn9	Atp1b1^tm1.1Zboro/Atp1b1^tm1.1Zboro Tg(Nkx2-1-cre)2Sand/0	involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6	MGI:5788016
cn10	Kmt2d^tm1.1Kaig/Kmt2d^tm1.1Kaig Tg(Nkx2-1-cre)2Sand/0	involves: C57BL/6	MGI:6515626
cn11	Igf1r^tm1Jcbr/Igf1r^tm1Jcbr Tg(Nkx2-1-cre)2Sand/0	involves: C57BL/6	MGI:5904181

Genotype
MGI:5517706

cn1

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Nkx2-1-cre)2Sand/0
• Genetic Background: B6.Cg-Pten^tm1Hwu Tg(Nkx2-1-cre)2Sand

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

endocrine/exocrine glands

abnormal thyroid gland morphology ( J:197590 )

• at P14, thyroid architecture is altered, with multilayered epithelial cells surrounding the colloid lumen and with some dysmorphic follicles containing abnormal material inside

abnormal thyroid follicle morphology ( J:197590 )

• dysmorphic follicles containing abnormal material inside and multiple degenerative follicles which have varying degrees of colloid depletion are seen at P14

enlarged thyroid gland ( J:197590 )

• increase in thyroid size is already seen at E15.5 and is striking by P14

thyroid gland hyperplasia ( J:197590 )

• increase in epithelial cell proliferation rate at E15.5 and P14

• Background Sensitivity: at P14, epithelial cell proliferation rates are higher on the congenic C57BL/6 background than on the BALB/c background

increased thyroid adenoma incidence ( J:197590 )

• at P14, thyroid structure is completely altered with multiple degenerative follicles, which have varying degrees of colloid depletion, resembling a follicular adenoma

homeostasis/metabolism

decreased thyroxine level ( J:197590 )

• decrease in T4 hormonal levels at P14

increased thyroid-stimulating hormone level ( J:197590 )

• increase in TSH at P14

mortality/aging

postnatal lethality, complete penetrance ( J:197590 )

• all mutants die before 2 weeks of age due to compression of the trachea and esophagus by the enlarged thyroid

neoplasm

increased thyroid adenoma incidence ( J:197590 )

• at P14, thyroid structure is completely altered with multiple degenerative follicles, which have varying degrees of colloid depletion, resembling a follicular adenoma

Genotype
MGI:5517709

cn2

• Allelic Composition: Pten^tm1Hwu/Pten⁺; Tg(Nkx2-1-cre)2Sand/0
• Genetic Background: B6.Cg-Pten^tm1Hwu Tg(Nkx2-1-cre)2Sand

endocrine/exocrine glands

abnormal thyroid gland morphology ( J:197590 )

• altered thyroid structure with normal areas that include colloid-filled follicles and normal areas with focal hyperplasia, polynuclear cells, small nonencapsulated areas of hypercellularity with solid and/or mircofollicular patterns and internal hemorrhage

increased thyroid tumor incidence ( J:197590 )

• 100% of mutants develop differentiated follicular tumors of the thyroid after about 2 years of age

homeostasis/metabolism

decreased thyroxine level ( J:197590 )

• P14 mutants show a mild decrease of T4 but normal TSH

neoplasm

increased thyroid tumor incidence ( J:197590 )

• 100% of mutants develop differentiated follicular tumors of the thyroid after about 2 years of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
follicular thyroid carcinoma		DOID:3962	OMIM:188470	J:197590

Genotype
MGI:5502638

cn3

• Allelic Composition: Stk3^tm1.1Jav/Stk3^tm1.1Jav; Stk4^tm1Kina/Stk4^tm1Kina; Tg(Nkx2-1-cre)2Sand/?
• Genetic Background: involves: 129 * C57BL/6

mortality/aging

postnatal lethality ( J:197340 )

• a markedly sick appearance at birth and almost all mice died within the first 15 d after birt

• born at normal Mendelian ratio

• lung size and dry lung weight were comparable between Mst1/2 dKO mice and control mice at E15.5 and E18.5

respiratory system

increased lung endothelial cell proliferation ( J:197340 )

• at E18.5, lungs showed a markedly increased number of proliferative cells and mildly diminished cell death

• no abnormal proliferation of mesenchymal cells

lung inflammation ( J:197340 )

• displayed spontaneous infiltration of inflammatory cells

• No bacteria and fungi were detected in lung sections or in cytospins of bronchoalveolar lavage fluid, ruling out the possibility of infection

abnormal lung development ( J:197340 )

• Lung Epithelial Cells Causes Abnormal Lung Maturation: Impaired Surfactant Homeostasis and Delayed Differentiation of Type I and II Pneumocytes

• vascularization was normal

abnormal pulmonary alveolus morphology ( J:197340 )

• reduced aerated space compacted with immature-looking cuboidal cells

primary atelectasis ( J:197340 )

• lung showed severe accumulation of inflammatory cells in the alveolar space and bronchiole with multiple atelectasis and emphysematous lesions

emphysema ( J:197340 )

• lung showed severe accumulation of inflammatory cells in the alveolar space and bronchiole with multiple atelectasis and emphysematous lesions

pulmonary hyaline membrane formation ( J:197340 )

• at around post natal day 5

immune system

lung inflammation ( J:197340 )

• displayed spontaneous infiltration of inflammatory cells

• No bacteria and fungi were detected in lung sections or in cytospins of bronchoalveolar lavage fluid, ruling out the possibility of infection

cellular

increased lung endothelial cell proliferation ( J:197340 )

• at E18.5, lungs showed a markedly increased number of proliferative cells and mildly diminished cell death

• no abnormal proliferation of mesenchymal cells

Genotype
MGI:5697928

cn4

• Allelic Composition: Dbx1^tm2Jcor/Dbx1^tm1Tmj; Tg(Nkx2-1-cre)2Sand/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

nervous system

abnormal hypothalamus secretion ( J:221571 )

♀ • attenuated response to predator (rat) odor is observed in females ( as measured by corticosterone levels in the lateral hypothalamus area) as compared to control females

♀ • males (either control or mutant) do not exhibit a response

abnormal action potential ( J:221571 )

• slices from the lateral hypothalamic area (LH) exhibit 85% lower spike density in low glucose

• slices from the lateral hypothalamic area (LH) exhibit 50% lower average spike frequency in high glucose

• however, glucose tolerance is not affected

behavior/neurological

abnormal response to novel odor ( J:221571 )

♀ • females exhibit a similar response following presentation with either rat or benign odor in contrast to controls

♀ • females exhibit fewer and shorter escape behaviors as compared to controls following presentation with rat odor

decreased food intake ( J:221571 )

♀ • females eat less than controls on a restricted diet

decreased compensatory feeding amount ( J:221571 )

♀ • decrease in amount of food consumed following a 12 hour fast is observed in females, but not males

♀ • however, daily food consumption is similar to controls

increased locomotor activity ( J:221571 )

♂ • activity, as determined by horizontal line crossings, is increased in males, but not in females

growth/size/body

decreased body weight ( J:221571 )

• decreased body weight in males, but not females, is observed after weaning

• females exhibit a decrease in body weight under restricted or high fat diets

adipose tissue

decreased percent body fat/body weight ( J:221571 )

♂ • males exhibit decrease in body fat composition after 7 weeks on high fat diet

Genotype
MGI:5517675

cn5

• Allelic Composition: Pten^tm1Hwu/Pten⁺; Tg(Nkx2-1-cre)2Sand/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6

endocrine/exocrine glands

abnormal thyroid follicle morphology ( J:197590 )

• enlarged follicles

enlarged thyroid gland ( J:197590 )

• mutants have an enlarged thyroid at 2 years of age and exhibit a goiter-like phenotype, but do not show development of tumors

thyroid gland hyperplasia ( J:197590 )

homeostasis/metabolism

increased thyroxine level ( J:197590 )

• P14 mutants show an increase in T4 levels

Genotype
MGI:5014514

cn6

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Nkx2-1-cre)2Sand/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:197590 )

N • Background Sensitivity: unlike on the congenic C57BL/6 background, mutants on the BALB/c background have normal T4 and TSH levels

decreased susceptibility to injury ( J:167962 )

• after naphthalene administration to induce lung injury, the proximal airway epithelium at 3 and 7 days post injury appears intact with no signs of injury

• after naphthalene administration to induce lung injury, the level of injury in the bronchial airway epithelium is reduced and repair is enhanced compared to controls

respiratory system

increased lung endothelial cell proliferation ( J:167962 )

• mutants exhibit an increase in the proliferation rate of the epithelial cells in E15.5 lungs

• expansion of epithelial cell populations occurs in multiple progenitor cell niches of the lungs including the tracheal basal cells in the proximal lung, the neuroepithelial bodies (NEB) in the distal bronchi and the progenitor cells occupying the bronchioalveolarduct junction (BADJ) region

abnormal lung morphology ( J:167962 )

• lungs exhibit increased cell proliferation and decreased apoptosis

• lungs at 8 weeks of age sometimes contain a mass consisting of epithelial cells (putative progenitor cell masses) around the BADJ area; masses are slow growing and are organized into ductlike structures

pulmonary hyperplasia ( J:167962 )

• progressive epithelial hyperplasia extending from the trachea to the small bronchioles is seen in the proximal lung epithelium from early stages of lung development and in adults

abnormal lung development ( J:167962 )

• marker analysis indicates a block in transition from precursor to terminally differentiated cell types indicating impaired epithelial cell fate determination in the lung

increased club cell number ( J:167962 )

• increase in number of Clara cells in the lungs and a decrease in the number of ciliated cells, the terminally differentiated progeny of Clara cells

cellular

increased lung endothelial cell proliferation ( J:167962 )

• mutants exhibit an increase in the proliferation rate of the epithelial cells in E15.5 lungs

• expansion of epithelial cell populations occurs in multiple progenitor cell niches of the lungs including the tracheal basal cells in the proximal lung, the neuroepithelial bodies (NEB) in the distal bronchi and the progenitor cells occupying the bronchioalveolarduct junction (BADJ) region

endocrine/exocrine glands

abnormal thyroid gland morphology ( J:197590 )

• Background Sensitivity: at P14, epithelial cell proliferation rates in the thyroid are lower on the mixed BALB/c background than on the congenic C57BL/6 background

• at P14, thyroid architecture is conserved but an increase in the number of epithelial cells along the follicles is seen, resembling a goiter disease

enlarged thyroid gland ( J:197590 )

thyroid gland hyperplasia ( J:197590 )

mortality/aging

mortality/aging ( J:197590 )

N • Background Sensitivity: mutants survive to adulthood on the BALB/c background without presenting any obvious pathological conditions unlike mice on the congenic C57BL/6 background

growth/size/body

pulmonary hyperplasia ( J:167962 )

• progressive epithelial hyperplasia extending from the trachea to the small bronchioles is seen in the proximal lung epithelium from early stages of lung development and in adults

Genotype
MGI:4836606

cn7

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Nkx2-1-cre)2Sand/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6

respiratory system

increased club cell number ( J:157922 )

• increase in the numbers of Clara cells in the lungs

Genotype
MGI:5902325

cn8

• Allelic Composition: Yy1^tm2.1Yshi/Yy1^tm2.1Yshi; Tg(Nkx2-1-cre)2Sand/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

mortality/aging

lethality at weaning, complete penetrance ( J:239777 )

• a small percentage of mutants survive up to weaning age

neonatal lethality, incomplete penetrance ( J:239777 )

• most mutants die at birth but some survive up to weaning age

neoplasm

increased blastoma incidence ( J:239777 )

• mice surviving to weaning exhibit characteristics of an evolving type I pleuropulmonary blastoma-like phenotype

respiratory system

lung cyst ( J:239777 )

• embryos exhibit cysts in the proximal region of lung lobes

• Type I and II pneumocytes, but not club and ciliated cells, are present along the cystic epithelium

• P21 lungs show multiocular cysts and variable septal thickness, small mesenchymal cells within the cyst walls, high proliferation levels of mesenchymal cells within the cystic wall

abnormal respiratory epithelium physiology ( J:239777 )

• increase in proliferation in E18.5 lungs

growth/size/body

lung cyst ( J:239777 )

• embryos exhibit cysts in the proximal region of lung lobes

• Type I and II pneumocytes, but not club and ciliated cells, are present along the cystic epithelium

• P21 lungs show multiocular cysts and variable septal thickness, small mesenchymal cells within the cyst walls, high proliferation levels of mesenchymal cells within the cystic wall

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pleuropulmonary blastoma		DOID:4769		J:239777

Genotype
MGI:5788016

cn9

• Allelic Composition: Atp1b1^tm1.1Zboro/Atp1b1^tm1.1Zboro; Tg(Nkx2-1-cre)2Sand/0
• Genetic Background: involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6

mortality/aging

postnatal lethality, complete penetrance ( J:233742 )

• pups die at 2-3 weeks of age

Genotype
MGI:6515626

cn10

• Allelic Composition: Kmt2d^tm1.1Kaig/Kmt2d^tm1.1Kaig; Tg(Nkx2-1-cre)2Sand/0
• Genetic Background: involves: C57BL/6

nervous system

impaired neuron differentiation ( J:301083 )

• marker analysis suggests that the development of GHRH-neurons, rather than just the expression of Ghrh, is impaired in mutant mice

• however, the number of AgRP-neurons is unchanged and neither Sf1+ or Trh+ cell numbers are altered

decreased neuron number ( J:301083 )

• growth hormone-releasing hormone (GHRH)-producing neurons expressing Ghrh and Th are reduced at E14.5-E15.5, indicating that development of GHRH-neurons is impaired

• mice show a reduction of GHRH-neurons at P65

homeostasis/metabolism

decreased circulating glucose level ( J:301083 )

cellular

impaired neuron differentiation ( J:301083 )

• marker analysis suggests that the development of GHRH-neurons, rather than just the expression of Ghrh, is impaired in mutant mice

• however, the number of AgRP-neurons is unchanged and neither Sf1+ or Trh+ cell numbers are altered

Genotype
MGI:5904181

cn11

• Allelic Composition: Igf1r^tm1Jcbr/Igf1r^tm1Jcbr; Tg(Nkx2-1-cre)2Sand/0
• Genetic Background: involves: C57BL/6

growth/size/body

increased body weight ( J:241923 )

• mice are significantly overweight after puberty

homeostasis/metabolism

abnormal response to injury ( J:241923 )

• mice show a delay in recovery of terminal bronchiolar epithelium after naphthalene treatment to induce club cell damage, with a delay in the differentiation/regeneration of club and ciliated cells

• mice show increased proliferation of bronchiolar epithelial cells during repair of the epithelium after naphthalene treatment to induce damage and club cell ablation

respiratory system

abnormal bronchiole epithelium morphology ( J:241923 )

• smaller epithelial cell size in terminal bronchioles

• lower proportion of Scgb1a1+ club cells

• distal bronchiolar epithelium shows morphological changes including lower cell density, flatter cells with elongated nuclei and frequent interruptions of normal columnar organization

• however, no gross morphological alterations are seen in AEC2 cells or in the surrounding alveolar parenchyma

• proliferation of airway club cells is enhanced in terminal bronchial epithelium