Phenotypes associated with this allele

• Allele Symbol: Zdhhc9^tm1Lex
• Allele Name: targeted mutation 1, Lexicon Pharmaceuticals
• Allele ID: MGI:5007410
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Zdhhc9^tm1Lex/Y Nras^tm1Tyj/Nras^tm1Tyj Tg(Mx1-cre)1Cgn/0	involves: 129S5/SvEvBrd * C57BL/6 * CBA	MGI:6771589
ot2	Zdhhc9^tm1Lex/Y	B6.129S5-Zdhhc9^tm1Lex	MGI:6315636
ot3	Zdhhc9^tm1Lex/Y	involves: 129S5/SvEvBrd * C57BL/6	MGI:6771586

Genotype
MGI:6771589

cn1

• Allelic Composition: Zdhhc9^tm1Lex/Y; Nras^tm1Tyj/Nras^tm1Tyj; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129S5/SvEvBrd * C57BL/6 * CBA

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

neoplasm

decreased leukemia incidence ( J:231488 )

• when bone marrow (BM) cells from polyinosinic-polycytidylic acid (pIpC)-treated mutant mice (CD45.2) are transplanted into lethally irradiated (CD45.1) recipient mice, less than 70% of recipients of mutant donor BM cells develop T cell acute lymphoblastic leukemia (T-ALL) with a slower progression and a median survival of 390 days post-transplantation versus 202 days for recipients of wild-type donor BM cells

• after oncogenic Nras activation by pIpC injection, mice develop a chronic myelomonocytic leukemia (CMML)-like disease with a significantly slower progression and a median survival of 173 days post-injection versus 152 days for control mice

Genotype
MGI:6315636

ot2

• Allelic Composition: Zdhhc9^tm1Lex/Y
• Genetic Background: B6.129S5-Zdhhc9^tm1Lex

behavior/neurological

impaired spatial learning ( J:268248 )

♂ • mice show impaired task acquisition in the Morris water maze indicating spatial learning deficits

♂ • however, mice exhibit normal behavior in the probe trial indicating normal reference memory

decreased anxiety-related response ( J:268248 )

♂ • in the open field test, mice spend more time in the inner zone and subsequently less time near the walls during the habituation period but not during the test period indicating reduced anxiety levels

♂ • in the elevated plus maze, mice spend more time exploring the more aversive open arms and the final third of the arms and less time exploring the closed arms

decreased startle reflex ( J:268248 )

♂ • mice exhibit reduced acoustic startle reactivity, beginning to show a startle response at decibel levels higher than 85 dB

♂ • however, mice display a similar pattern of prepulse inhibition as wild-type mice, indicating normal sensorimotor gating and hearing ability

growth/size/body

decreased body weight ( J:268248 )

♂ • mice are lighter than wild-type mice

muscle

hypotonia ( J:268248 )

♂ • in the hanging wire test, mice spend a shorter period of time hanging on the wire, indicative of hypotonia

♂ • however, mice perform similar to wild-type mice on the rotarod test

nervous system

decreased corpus callosum size ( J:268248 )

♂ • mice have on average 30% reduction in the total volume of the corpus callosum

♂ • however, no change in hippocampus size is seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
syndromic X-linked intellectual disability Raymond type		DOID:0060824	OMIM:300799	J:268248

Genotype
MGI:6771586

ot3

• Allelic Composition: Zdhhc9^tm1Lex/Y
• Genetic Background: involves: 129S5/SvEvBrd * C57BL/6

hematopoietic system

hematopoietic system phenotype ( J:231488 )

N • under homeostatic conditions, hematopoiesis is normal with no significant changes in liver, spleen and thymus weight, absolute numbers of leukocytes, erythrocytes, platelets and hemoglobin level in peripheral blood, or bone marrow (BM) and spleen cellularity

N • normal frequencies of LSKs (Lineage-/Sca1+/c-Kit+), SLAMs (CD150+/CD48-/Lineage-/Sca1+/c-Kit+), B cells (CD19+and B220+), myeloid cells (Mac-1+ and Gr-1+) and T cells (CD3+) in BM

N • normal clonogenic potential of hematopoietic stem cells (HSCs) and progenitors

abnormal leukocyte physiology ( J:231488 )

• after a single dose of 5-fluorouracil (150 mg/kg) treatment, mice show a slightly faster recovery of peripheral leukocytes than wild-type controls

• after two doses 5-fluorouracil, reduction in peripheral leukocyte count is moderately but significantly slower than in wild-type controls

abnormal bone marrow cell physiology ( J:231488 )

• Ras palmitoylation is significantly reduced but not completely abolished in bone marrow cells from mutant mice, as shown by an acyl-biotinyl exchange assay

homeostasis/metabolism

decreased susceptibility to xenobiotic induced morbidity/mortality ( J:231488 )

• after two doses 5-fluorouracil treatment, death is moderately but significantly slower than in wild-type controls

decreased physiological sensitivity to xenobiotic ( J:231488 )

• after two doses 5-fluorouracil treatment, reduction in peripheral leukocyte count is moderately but significantly slower than in wild-type controls

immune system

abnormal leukocyte physiology ( J:231488 )

• after a single dose of 5-fluorouracil (150 mg/kg) treatment, mice show a slightly faster recovery of peripheral leukocytes than wild-type controls

• after two doses 5-fluorouracil, reduction in peripheral leukocyte count is moderately but significantly slower than in wild-type controls

mortality/aging

decreased susceptibility to xenobiotic induced morbidity/mortality ( J:231488 )

• after two doses 5-fluorouracil treatment, death is moderately but significantly slower than in wild-type controls