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The sanctuary doubles as a home for the owner, who was asleep on the second floor when flames broke out, firefighters said. They said the man was only alerted to the fire by peacocks squawking outside.
The man escaped the flames uninjured.
Firefighters said at any given time the sanctuary can be home to as many as 300 to 350 animals ranging from dogs and cats to pigs and swans.
Neighbor Denis Moredo said he heard an "explosion" and then saw flames coming from his neighbor's home. He said he also saw a swan running across the road to escape the blaze.
"All of the sudden I see these flames just blazing up 30 feet high. And I went out with my dad. Our first instinct was to go see if the owner was OK," Moredo said.
Firefighters said by the time they arrived, the wood-framed home was completely involved. The sanctuary owner said he tried to rescue his dogs, which were asleep with him in bed, but only managed to pull one out alive.
It is unknown how many animals perished in the fire, but it is believed to be dozens, including dogs, snakes and four giant tortoises.
"All of them are gone. They're all burnt. Everything is gone. His home is gone. He ran out of the house with just himself," said neighbor Rose Arnemann.
The homeowner told firefighters he does not have insurance.