Phenotypes associated with this allele

• Allele Symbol: Loxl2^tm1.2Acan
• Allele Name: targeted mutation 1.2, Amparo Cano
• Allele ID: MGI:5750228
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Loxl2^tm1.2Acan/Loxl2^tm1.2Acan	Not Specified	MGI:5766517

Genotype
MGI:5766517

hm1

• Allelic Composition: Loxl2^tm1.2Acan/Loxl2^tm1.2Acan
• Genetic Background: Not Specified

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

mortality/aging

lethality during fetal growth through weaning, incomplete penetrance ( J:220689 )

• although obtained at normal Mendelian ratios at E13.5, homozygotes are present at ~2-fold lower frequency (10.7% vs 25%) after weaning

• 8.9% are dead at P1, likely due to congenital hearts defects and/or altered liver tissue homeostasis

homeostasis/metabolism

cyanosis ( J:220689 )

• at P1, some neonates display a cyanotic appearance and die within a few hours

decreased incidence of tumors by chemical induction ( J:220689 )

• following DMBA-TPA treatment, homozygotes show a reduction of tumor burden relative to wild-type controls

• however, onset of lesion formation after DMBA-TPA treatment is similar to that in controls (>8 weeks post initiation)

cardiovascular system

abnormal liver vasculature morphology ( J:220689 )

• 2 of 8 dead neonates exhibit distended hepatic blood vessels

abnormal interventricular septum morphology ( J:220689 )

• 2 of 8 dead neonates exhibit disrupted ventricular septa formation

liver/biliary system

abnormal liver vasculature morphology ( J:220689 )

• 2 of 8 dead neonates exhibit distended hepatic blood vessels

neoplasm

decreased incidence of tumors by chemical induction ( J:220689 )

• following DMBA-TPA treatment, homozygotes show a reduction of tumor burden relative to wild-type controls

• however, onset of lesion formation after DMBA-TPA treatment is similar to that in controls (>8 weeks post initiation)

abnormal tumor pathology ( J:220689 )

• following DMBA-TPA treatment, only 2.8% (two of 72) neoplastic skin lesions (papillomas) progress to squamous cell carcinoma (SCC) relative to 7.7% (seven of 90) of lesions in wild-type controls

• reduced malignant progression of papillomas correlates with increased epidermal differentiation, as shown by upregulated expression of early and late differentiation markers such as K1, loricrin and involucrin

decreased tumor growth/size ( J:220689 )

• at 28 weeks post-DMBA application, most neoplastic lesions remain smaller than 4 mm, with only 25% of lesions reaching >6 mm in size relative to 50% of neoplasias in wild-type controls

immune system

decreased inflammatory response ( J:220689 )

• decreased inflammatory infiltration in DMBA-TPA induced papilloma lesions, with strong downregulation of S100A8 and S100A9 cytokine transcripts relative to wild-type controls

cellular

abnormal keratinocyte differentiation ( J:220689 )

• in vitro, primary keratinocytes derived from newborn homozygotes exhibit increased protein levels of loricrin and suprabasal cytokeratins relative to controls

• however, no major changes in Ca2+ induced differentiation and cell adhesion to a collagen IV matrix are observed

integument

abnormal keratinocyte differentiation ( J:220689 )

• in vitro, primary keratinocytes derived from newborn homozygotes exhibit increased protein levels of loricrin and suprabasal cytokeratins relative to controls

• however, no major changes in Ca2+ induced differentiation and cell adhesion to a collagen IV matrix are observed