Phenotypes associated with this allele

• Allele Symbol: Nkx3-1^tm1Hha
• Allele Name: targeted mutation 1, Hans-Henning Arnold
• Allele ID: MGI:1928654
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nkx3-1^tm1Hha/Nkx3-1^tm1Hha	involves: 129S4/SvJae * C57BL/6	MGI:2175150
ht2	Nkx3-1^tm1Hha/Nkx3-1^+	involves: 129S4/SvJae * C57BL/6	MGI:2175151
cx3	Nkx3-2^tm1Bobh/Nkx3-2^tm1Bobh Nkx3-1^tm1Hha/Nkx3-1^tm1Hha	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:3608887

Genotype
MGI:2175150

hm1

• Allelic Composition: Nkx3-1^tm1Hha/Nkx3-1^tm1Hha
• Genetic Background: involves: 129S4/SvJae * C57BL/6

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

behavior/neurological

reduced male mating frequency ( J:63764 )

♂ • homozygotes are developmentally normal and fertile; however, mutant males display inadequate plug formation upon copulation with advancing age

endocrine/exocrine glands

abnormal minor salivary gland morphology ( J:63764 )

• homozygotes display a marked size reduction in all three minor salivary glands, with smaller apical mucous end-pieces relative to wild-type mice

abnormal palatine gland morphology ( J:63764 )

• the mutant palatine gland is significantly smaller; similar size reductions are noted in the glandula lingualis and glandula buccalis

abnormal salivary gland duct morphology ( J:63764 )

• in addition, the ductal system exhibits irregular branching esp. in the glandula palatina and glandula lingualis

narrow salivary ducts ( J:63764 )

• in homozygotes, the ducts of minor salivary glands appear smaller in diameter and the diameter of the ductal lumen is reduced by thicker epithelium

• smaller ducts with reduced internal lumens are particularly pronounced in the palatine and lingual glands

salivary gland epithelial hyperplasia ( J:63764 )

• adult homozygotes show evidence for salivary gland epithelial hyperplasia, although not as severe as in the prostate

small salivary gland ( J:63764 )

• homozygotes exhibit significantly smaller minor salivary glands (i.e. glandula buccalis, glandula palatina, and glandula lingualis) relative to wild-type mice

decreased salivation ( J:63764 )

• unlike wild-type mice, homozygotes frequently contain relatively dry food residues in their mouths, suggesting impaired mucous salivary production

abnormal bulbourethral gland morphology ( J:63764 )

♂ • at 4 months, mutant BUGs exhibit an increased number of nuclei, suggesting hyperproliferation of epithelial cells

abnormal bulbourethral gland development ( J:63764 )

• at 4 months, mutant BUGs show a dramatic reduction of mucin-producing cells and contain primarily ductal cells, suggesting abnormal cell differentiation or an imbalance in cell growth

small bulbourethral gland ( J:63764 )

♂ • at 3 months, homozygotes exhibit a significantly smaller bulbourethral glands (BUGs) relative to wild-type mice

abnormal prostate gland morphology ( J:63764 )

♂ • homozygotes invariably display prostate epithelial hyperplasia in the absence of overt prostate tumors during the observation period of >1 year

prostate gland anterior lobe hyperplasia ( J:63764 )

♂ • as early as 2 months, homozygotes exhibit progressive prostate epithelial hyperplasia in the anterior lobes

small prostate gland anterior lobe ( J:63764 )

♂ • at 3 months, homozygotes exhibit a moderate size reduction of the anterior prostate

abnormal prostate gland branching morphogenesis ( J:63764 )

♂ • at 3 months, homozygotes exhibit fewer but enlarged prostatic ducts in the anterior prostate and other prostatic lobes

decreased ductal branching in the coagulating gland ( J:63764 )

♂ • at 3 months, homozygotes exhibit fewer but enlarged prostatic ducts in the anterior prostate

prostate gland dorsolateral lobe hyperplasia ( J:63764 )

♂ • as early as 2 months, homozygotes exhibit progressive prostate epithelial hyperplasia in the dorsolateral lobes

♂ • however, no hyperplasia is noted in ventral prostatic lobes

decreased prostate gland duct number ( J:63764 )

♂ • although adult homozygotes exhibit all three prostatic lobes, the number of prostatic ducts appears reduced relative to heterozygous and wild-type mice

♂ • in addition, individual ducts appear enlarged, suggesting defective ductal branching

abnormal prostate gland epithelium morphology ( J:63764 )

♂ • adult homozygotes show progressive dysplastic changes in the duct epithelium of the anterior and dorsolateral prostate, resulting in a severely dysplastic, multi-layered epithelium with little secreted fluid in the duct lumen at 10 months

reproductive system

abnormal bulbourethral gland morphology ( J:63764 )

♂ • at 4 months, mutant BUGs exhibit an increased number of nuclei, suggesting hyperproliferation of epithelial cells

abnormal bulbourethral gland development ( J:63764 )

• at 4 months, mutant BUGs show a dramatic reduction of mucin-producing cells and contain primarily ductal cells, suggesting abnormal cell differentiation or an imbalance in cell growth

small bulbourethral gland ( J:63764 )

♂ • at 3 months, homozygotes exhibit a significantly smaller bulbourethral glands (BUGs) relative to wild-type mice

abnormal prostate gland morphology ( J:63764 )

♂ • homozygotes invariably display prostate epithelial hyperplasia in the absence of overt prostate tumors during the observation period of >1 year

prostate gland anterior lobe hyperplasia ( J:63764 )

♂ • as early as 2 months, homozygotes exhibit progressive prostate epithelial hyperplasia in the anterior lobes

small prostate gland anterior lobe ( J:63764 )

♂ • at 3 months, homozygotes exhibit a moderate size reduction of the anterior prostate

abnormal prostate gland branching morphogenesis ( J:63764 )

♂ • at 3 months, homozygotes exhibit fewer but enlarged prostatic ducts in the anterior prostate and other prostatic lobes

decreased ductal branching in the coagulating gland ( J:63764 )

♂ • at 3 months, homozygotes exhibit fewer but enlarged prostatic ducts in the anterior prostate

prostate gland dorsolateral lobe hyperplasia ( J:63764 )

♂ • as early as 2 months, homozygotes exhibit progressive prostate epithelial hyperplasia in the dorsolateral lobes

♂ • however, no hyperplasia is noted in ventral prostatic lobes

decreased prostate gland duct number ( J:63764 )

♂ • although adult homozygotes exhibit all three prostatic lobes, the number of prostatic ducts appears reduced relative to heterozygous and wild-type mice

♂ • in addition, individual ducts appear enlarged, suggesting defective ductal branching

abnormal prostate gland epithelium morphology ( J:63764 )

♂ • adult homozygotes show progressive dysplastic changes in the duct epithelium of the anterior and dorsolateral prostate, resulting in a severely dysplastic, multi-layered epithelium with little secreted fluid in the duct lumen at 10 months

digestive/alimentary system

abnormal minor salivary gland morphology ( J:63764 )

• homozygotes display a marked size reduction in all three minor salivary glands, with smaller apical mucous end-pieces relative to wild-type mice

abnormal palatine gland morphology ( J:63764 )

• the mutant palatine gland is significantly smaller; similar size reductions are noted in the glandula lingualis and glandula buccalis

abnormal salivary gland duct morphology ( J:63764 )

• in addition, the ductal system exhibits irregular branching esp. in the glandula palatina and glandula lingualis

narrow salivary ducts ( J:63764 )

• in homozygotes, the ducts of minor salivary glands appear smaller in diameter and the diameter of the ductal lumen is reduced by thicker epithelium

• smaller ducts with reduced internal lumens are particularly pronounced in the palatine and lingual glands

salivary gland epithelial hyperplasia ( J:63764 )

• adult homozygotes show evidence for salivary gland epithelial hyperplasia, although not as severe as in the prostate

small salivary gland ( J:63764 )

• homozygotes exhibit significantly smaller minor salivary glands (i.e. glandula buccalis, glandula palatina, and glandula lingualis) relative to wild-type mice

decreased salivation ( J:63764 )

• unlike wild-type mice, homozygotes frequently contain relatively dry food residues in their mouths, suggesting impaired mucous salivary production

cellular

increased cell proliferation ( J:63764 )

• in mutant glandula palatina and glandula lingualis, the epithelium appears significantly thicker, suggesting epithelial hyperproliferation

embryo

embryo phenotype ( J:63764 )

N • surpisingly, homozygotes exhibit no sclerotomal defects and develop into adulthood with no apparent skeletal abnormalities

homeostasis/metabolism

decreased salivation ( J:63764 )

• unlike wild-type mice, homozygotes frequently contain relatively dry food residues in their mouths, suggesting impaired mucous salivary production

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:63764

Genotype
MGI:2175151

ht2

• Allelic Composition: Nkx3-1^tm1Hha/Nkx3-1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

reproductive system

abnormal prostate gland anterior lobe morphology ( J:63764 )

♂ • at 10 months, heterozygotes exhibit dysplastic changes in the anterior prostate, although of reduced severity relative to homozygotes

prostate gland anterior lobe hyperplasia ( J:63764 )

♂ • at 2 months, heterozygotes exhibit a normal ductal epithelium in the anterior prostate (AP) relative to wild-type mice; however, moderate AP hyperplasia is observed at 10 months

prostate gland dorsolateral lobe hyperplasia ( J:63764 )

♂ • by 10 months, heterozygotes also exhibit epithelial hyperplasia in the dorsolateral prostate, although of reduced severity relative to homozygotes

♂ • similar to homozygotes, no hyperplasia is observed in heterozygous ventral prostatic lobes

endocrine/exocrine glands

abnormal prostate gland anterior lobe morphology ( J:63764 )

♂ • at 10 months, heterozygotes exhibit dysplastic changes in the anterior prostate, although of reduced severity relative to homozygotes

prostate gland anterior lobe hyperplasia ( J:63764 )

♂ • at 2 months, heterozygotes exhibit a normal ductal epithelium in the anterior prostate (AP) relative to wild-type mice; however, moderate AP hyperplasia is observed at 10 months

prostate gland dorsolateral lobe hyperplasia ( J:63764 )

♂ • by 10 months, heterozygotes also exhibit epithelial hyperplasia in the dorsolateral prostate, although of reduced severity relative to homozygotes

♂ • similar to homozygotes, no hyperplasia is observed in heterozygous ventral prostatic lobes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:63764

Genotype
MGI:3608887

cx3

• Allelic Composition: Nkx3-2^tm1Bobh/Nkx3-2^tm1Bobh; Nkx3-1^tm1Hha/Nkx3-1^tm1Hha
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:79198 )

• at E12.5, double homozygotes are present at the expected Mendelian frequency

• however, only ~50% and 15% of the expected number are obtained at E14.5 and E17.5, respectively, with a gradually increasing embryo loss noted between E13.5 and E17.5

• no double homozygotes are recovered alive after E17.5

skeleton

abnormal axial skeleton morphology ( J:79198 )

• at E17.5, the axial skeleton of double homozygotes appears even shorter than that of Bapx1^tm1Bobh homozygotes

abnormal rib morphology ( J:79198 )

• at E17.5, double homozygotes exhibit even more tightly spaced ribs than Bapx1^tm1Bobh homozygotes

abnormal cervical atlas morphology ( J:79198 )

• at E17.5, the double mutant atlas is reduced to only the lateral parts lacking most of the cartilage that gives rise to the vertebral body

abnormal lumbar vertebrae morphology ( J:79198 )

• at E17.5, double mutant lumbar vertebrae completely lack the normal dorsal processes observed as bifurcations in Bapx1^tm1Bobh homozygotes

abnormal vertebrae development ( J:79198 )

• at E17.5, double homozygotes show an enhanced reduction or loss of ventro-medial cartilaginous material in all cervical vertebrae relative to Bapx1^tm1Bobh homozygotes

abnormal vertebral body morphology ( J:79198 )

• at E17.5, double homozygotes lack the central ossification centers in cervical vertebrae, with the atlas being most severely affected; this defect is less obvious in thoracic and lumbar vertebrae

abnormal cartilage development ( J:79198 )

• at E14.5, double homozygotes exhibit a severe reduction in the number of chondrogenic cells around the notochord, with only few scattered cells present at the cervical level but no signs of cartilage formation; at lumbar level, chondrogenic cell numbers are also further reduced relative to Bapx1^tm1Bobh homozygotes

• except for the region of pedicles essentially no cartilage is formed in the vertebral anlagen of double homozygotes

abnormal sclerotome morphology ( J:79198 )

• double homozygotes exhibit exacerbated sclerotomal defects in cervical and lumbar segments relative to Bapx1^tm1Bobh homozygotes

limbs/digits/tail

kinked tail ( J:79198 )

• at E17.5, double homozygotes display severely kinked tails relative to Bapx1^tm1Bobh homozygotes